Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13883/full. Transporters are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ligand‐gated ion channels, voltage‐gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.The Concise Guide to PHARMACOLOGY 2017/18 provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands ( Cellular membranes are hydrophobic and, therefore, effective barriers to separate them allowing the formation of gradients, which can be exploited, for example, in the generation of energy. Membrane transporters carry solutes across cell membranes, which would otherwise be impermeable to them. The energy required for active transport processes is obtained from ATP turnover or by exploiting ion gradients.ATP‐driven transporters can be divided into three major classes: P‐type ATPases; F‐type or V‐type ATPases and ATP‐binding cassette transporters. The first of these, P‐type ATPases, are multimeric proteins, which transport (primarily) inorganic cations. The second, F‐type or V‐type ATPases, are proton‐coupled motors, which can function either as transporters or as motors. Last, are ATP‐binding cassette transporters, heavily involved in drug disposition as well as transporting endogenous solutes.The second largest family of membraine proteins in the human genome, after the G protein‐coupled receptors, are the SLC solute carrier family. Within the solute carrier family, there are not only a great variety of solutes transported, from simple inorganic ions to amino acids and sugars to relatively complex organic molecules like haem. The solute carrier family includes 52 families of almost 400 members. Many of these overlap in terms of the solutes that they carry. For example, amino acids accumulation is mediated by members of the SLC1, SLC3/7, SLC6, SLC15, SLC16, SLC17, SLC32, SLC36, SLC38 and SLC43 families. Further members of the SLC superfamily regulate ion fluxes at the plasma membrane, or solute transport into and out of cellular organelles. Some SLC family members remain orphan transporters, in as much as a physiological function has yet to be dtermined. Within the SLC superfamily, there is an abundance in diversity of structure. Two families (SLC3 and SLC7) only generate functional transporters as heteromeric partners, where one partner is a single TM domain protein. Membrane topology predictions for other families suggest 3,4,6,7,8,9,10,11,12,13 or 14 TM domains. The SLC transporters include members which function as antiports, where solute movement in one direction is balanced by a solute moving in the reverse direction. Symports allow concentration gradients of one solute to allow movement of a second solute across a membrane. A third, relatively small group are equilibrative transporters, which allow solutes to travel across membranes down their concentration gradients. A more complex family of transporters, the SLC27 fatty acid transporters also express enzymatic function. Many of the transporters also express electrogenic properties of ion channels.Orphan or poorly characterized SLC22 family members– ATP‐binding cassette transporters are ubiquitous membrane proteins characterized by active ATP‐dependent movement of a range of substrates, including ions, lipids, peptides, steroids. Individual subunits are typically made up of two groups of 6TM‐spanning domains, with two nucleotide‐binding domains (NBD). The majority of eukaryotic ABC transporters are ŚfullŠ transporters incorporating both TM and NBD entities. Some ABCs, notably the ABCD and ABCG families are half‐transporters with only a single membrane spanning domain and one NBD, and are only functional as homo‐ or heterodimers. Eukaryotic ABC transporters convey substrates from the cytoplasm, either out of the cell or into intracellular organelles. Their role in the efflux of exogenous compounds, notably chemotherapeutic agents, has led to considerable interest.ENSMUSG00000062017); Abca15 (ENSMUSG00000054746); Abca16 (ENSMUSG00000051900) and Abca17 (ENSMUSG00000035435).A number of structural analogues are not found in man: Abca14  and ABCC9  are unusual in that they lack transport capacity but regulate the activity of particular K+ channels (Kir6.1‐6.2), conferring nucleotide sensitivity to these channels to generate the canonical KATP channels. ABCC13 (ENSG00000155288) is a possible pseudogene.ABCC7  is located at the lysosome and is in involved in the transport of vitamin B12  from lysosomes into the cytosol [105].ABCD4 ; ABCF1; ABCF2 and ABCF3(Q9NUQ8).A further group of ABC transporter‐like proteins have been identified to lack membrane spanning regions and are not believed to be functional transporters, but appear to have a role in protein translation [[PMID:26517910]Baker A et al. (2015) Peroxisomal ABC transporters: functions and mechanism. Biochem Soc Trans 43: 959‐65 [PMID:26517899]Beis, K. (2015) Structural basis for the mechanism of ABC transporters. Biochem Soc Trans 43: 889‐93 [PMID:26499806]Chen Z et al. (2016) Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett 370: 153‐64 [PMID:21488864]Kemp S et al. (2011) Mammalian peroxisomal ABC transporters: from endogenous substrates to pathology and clinical significance. Br. J. Pharmacol. 164: 1753‐66 [PMID:21175590]Kerr ID et al. (2011) The ABCG family of membrane‐associated transporters: you don't have to be big to be mighty. Br. J. Pharmacol. 164: 1767‐79 [PMID:28410994]Kloudova A et al. (2017) The Role of Oxysterols in Human Cancer. Trends Endocrinol Metab 28: 485‐496 [PMID:24746984]López‐Marqués RL et al. (2015) Structure and mechanism of ATP‐dependent phospholipid transporters. Biochim. Biophys. Acta 1850: 461‐475 [PMID:27659854]Neul C et al. (2016) Impact of Membrane Drug Transporters on Resistance to Small‐Molecule Tyrosine Kinase Inhibitors. Trends Pharmacol Sci 37: 904‐932 [PMID:28005280]Pena‐Solorzano D. (2016) ABCG2/BCRP: Specific and Nonspecific Modulators. Med Res Rev [PMID:28245962]Vauthier V et al. (2017) Targeted pharmacotherapies for defective ABC transporters. Biochem Pharmacol 136: 1‐11 1 or V1) and a membrane complex (Fo or Vo). Within each ATPase complex, the two individual sectors appear to function as connected opposing rotary motors, coupling catalysis of ATP synthesis or hydrolysis to proton transport. Both the F‐type and V‐type ATPases have been assigned enzyme commission number E.C. 3.6.3.14The F‐type (ATP synthase) and the V‐type (vacuolar or vesicular proton pump) ATPases, although having distinct subcellular locations and roles, exhibit marked similarities in subunit structure and mechanism. They are both composed of a ‘soluble’ complex (termed F+‐transporting), is a mitochondrial membrane‐associated multimeric complex consisting of two domains, an F0 channel domain in the membrane and an F1 domain extending into the lumen. Proton transport across the inner mitochondrial membrane is used to drive the synthesis of ATP, although it is also possible for the enzyme to function as an ATPase. The ATP5O subunit ), acts as a connector between F1 and F0 motors.The F‐type ATPase, also known as ATP synthase or ATP phosphohydrolase .TheVonline database.Information on members of this family may be found in the [PMID:25838297]Brandt K et al. (2015) Hybrid rotors in F1F(o) ATP synthases: subunit composition, distribution, and physiological significance. Biol Chem 396: 1031‐42 [PMID:26140992]Krah A. (2015) Linking structural features from mitochondrial and bacterial F‐type ATP synthases to their distinct mechanisms of ATPase inhibition. Prog Biophys Mol Biol 119: 94‐102 [PMID:24508215]Marshansky V et al. (2014) Eukaryotic V‐ATPase: novel structural findings and functional insights. Biochim Biophys Acta 1837: 857‐79 [PMID:28424741]Noji H et al. (2017) Catalytic robustness and torque generation of the F1‐ATPase. Biophys Rev 9: 103‐118 [PMID:24094404]Okuno D et al. (2013) Single‐molecule analysis of the rotation of F(1)‐ATPase under high hydrostatic pressure. Biophys J 105: 1635‐42 Phosphorylation‐type ATPases (EC 3.6.3.‐) are associated with membranes and the transport of ions or phospholipids. Characteristics of the family are the transient phosphorylation of the transporters at an aspartate residue and the interconversion between E1 and E2 conformations in the activity cycle of the transporters, taken to represent ‘half‐channels’ facing the cytoplasm and extracellular/luminal side of the membrane, respectively.Sequence analysis across multiple species allows the definition of five subfamilies, P1‐P5. The P1 subfamily includes heavy metal pumps, such as the copper ATPases. The P2 subfamily includes calcium, sodium/potassium and proton/potassium pumps. The P4 and P5 subfamilies include putative phospholipid flippases.+/K+‐ATPase is an integral membrane protein which regulates the membrane potential of the cell by maintaining gradients of Na+ and K+ ions across the plasma membrane, also making a small, direct contribution to membrane potential, particularly in cardiac cells. For every molecule of ATP hydrolysed, the Na+/K+‐ATPase extrudes three Na+ ions and imports two K+ ions. The active transporter is a heteromultimer with incompletely defined stoichiometry, possibly as tetramers of heterodimers, each consisting of one of four large, ten TM domain catalytic α subunits and one of three smaller, single TM domain glycoprotein β‐subunits (see table). Additional protein partners known as FXYD proteins  appear to associate with and regulate the activity of the pump.The cell‐surface Naonline database.Information on members of this family may be found in the +/K+‐ATPases are inhibited by ouabain and cardiac glycosides, such as digoxin, as well as potentially endogenous cardiotonic steroids [29].Na2+‐ATPase (SERCA) is an intracellular membrane‐associated pump for sequestering calcium from the cytosol into intracellular organelles, usually associated with the recovery phase following excitation of muscle and nerves.The sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase (PMCA) is a cell‐surface pump for extruding calcium from the cytosol, usually associated with the recovery phase following excitation of cells. The active pump is a homodimer, each subunit of which is made up of ten TM segments, with cytosolic C‐ and N‐termini and two large intracellular loops.The plasma membrane Ca2+‐ATPases (SPCA) allow accumulation of calcium and manganese in the Golgi apparatus.Secretory pathway Caonline database.Information on members of this family may be found in the ochratoxin A has been described to activate SERCA in kidney microsomes [99]. Cyclopiazonic acid [482], thapsigargin[359] and BHQ are widely employed to block SERCA. Thapsigargin has also been described to block the TRPV1 vanilloid receptor [535].The fungal toxin 2+ while SERCA transports 2 Ca2+.The stoichiometry of flux through the PMCA differs from SERCA, with the PMCA transporting 1 Ca256].Loss‐of‐function mutations in SPCA1 appear to underlie Hailey‐Hailey disease .The Honline database.Information on members of this family may be found in the +/K+‐ATPase is inhibited by proton pump inhibitors used for treating excessive gastric acid secretion, including dexlansoprazole and a metabolite of esomeprazole.The gastric HATOX1, O00244).Copper‐transporting ATPases convey copper ions across cell‐surface and intracellular membranes. They consist of eight TM domains and associate with multiple copper chaperone proteins , ATP13A2 (Q9NQ11), ATP13A3 (Q9H7F0), ATP13A4 (Q4VNC1) and ATP13A5(Q4VNC0).A further series of structurally‐related proteins have been identified in the human genome, with as yet undefined function, including [PMID:26791490]Aperia A et al. (2016) Na+‐K+‐ATPase, a new class of plasma membrane receptors. Am J Physiol Cell Physiol 310: C491‐5 [PMID:27480928]Brini M et al. (2017) The plasma membrane calcium pumps: focus on the role in (neuro)pathology. Biochem Biophys Res Commun 483: 1116‐1124 [PMID:28625348]Bruce, JIE. (2017) Metabolic regulation of the PMCA: Role in cell death and survival. Cell Calcium [PMID:27553475]Diederich M. (2017) Cardiac glycosides: From molecular targets to immunogenic cell death. Biochem Pharmacol 125: 1‐11 [PMID:26658643]Dubois C et al. (2016) CThe calcium‐signaling toolkit: Updates needed. Biochim Biophys Acta 1863: 1337‐43 [PMID:25535949]Krebs J. (2015) The plethora of PMCA isoforms: Alternative splicing and differential expression. Biochim Biophys Acta 1853: 2018‐24 [PMID:26820758]Little R et al. (2016) Plasma membrane calcium ATPases (PMCAs) as potential targets for the treatment of essential hypertension. Pharmacol Ther 159: 23‐34 [PMID:24746984]Lopez‐Marques RL et al. (2015) Structure and mechanism of ATP‐dependent phospholipid transporters. Biochim Biophys Acta 1850: 461‐75 [PMID:26422816]Migocka M. (2015) Copper‐transporting ATPases: The evolutionarily conserved machineries for balancing copper in living systems. IUBMB Life 67: 737‐45 [PMID:26707182]Padanyi R et al. (2016) Multifaceted plasma membrane Ca(2+) pumps: From structure to intracellular Ca(2+) handling and cancer. Biochim Biophys Acta 1863: 1351‐63 [PMID:27528189]Pomorski TG et al. (2016) Lipid somersaults: Uncovering the mechanisms of protein‐mediated lipid flipping. Prog Lipid Res 64: 69‐84 [PMID:25631710]Retamales‐Ortega R et al. (2016) P2C‐Type ATPases and Their Regulation. Mol Neurobiol 53: 1343‐54 [PMID:25998731]Strehler EE. (2015) Plasma membrane calcium ATPases: From generic Ca(2+) sump pumps to versatile systems for fine‐tuning cellular Ca(2.). Biochem. Biophys. Res. Commun. 460: 26‐33 [PMID:28164426]Tadini‐Buoninsegni F et al. (2017) Mechanisms of charge transfer in human copper ATPases ATP7A and ATP7B. IUBMB Life 69: 218‐225 The Major Facilitator superfamily (MFS) of transporters was initially characterised as prokaryotic sugar transporters.[PMID:27752944]Loscher, W et al. (2016) Synaptic Vesicle Glycoprotein 2A Ligands in the Treatment of Epilepsy and Beyond. CNS Drugs 30: 1055‐1077 [PMID:24102679]Mendoza‐Torreblanca, JG et al. (2013) Synaptic vesicle protein 2A: basic facts and role in synaptic function. Eur J Neurosci 38: 3529‐39 The SLC superfamily of solute carriers is the second largest family of membrane proteins after G protein‐coupled receptors, but with a great deal fewer therapeutic drugs that exploit them. As with the ABC transporters, however, they play a major role in drug disposition and so can be hugely influential in determining the clinical efficacy of particular drugs.48 families are identified on the basis of sequence similarities, but many of them overlap in terms of the solutes that they carry. For example, amino acid accumulation is mediated by members of the SLC1, SLC3/7, SLC6, SLC15, SLC16, SLC17, SLC32, SLC36, SLC38 and SLC43. Further members of the SLC superfamily regulate ion fluxes at the plasma membrane, or solute transport into and out of cellular organelles.Within the SLC superfamily, there is an abundance in diversity of structure. Two families (SLC3 and SLC7) only generate functional transporters as heteromeric partners, where one partner is a single TM domain protein. Membrane topology predictions for other families suggest 3, 4 6, 7, 8, 9, 10, 11, 12, 13, or 14 TM domains. Functionally, members may be divided into those dependent on gradients of ions , exchange of solutes or simple equilibrative gating. For many members, the stoichiometry of transport is not yet established. Furthermore, one family of transporters also possess enzymatic activity (SLC27), while many members function as ion channels (e.g. SLC1A7/EAAT5), which increases the complexity of function of the SLC superfamily.[PMID:27118869]Bhutia, YD et al. (2016) SLC transporters as a novel class of tumour suppressors: identity, function and molecular mechanisms. Biochem J 473: 1113‐24 [PMID:26232220]Cesar‐Razquin, et al. (2015) A Call for Systematic Research on Solute Carriers. Cell 162: 478‐87 [PMID:27672436]Colas, C et al. (2016) SLC Transporters: Structure, Function, and Drug Discovery. Medchemcomm 7: 1069‐1081 [PMID:26111766]Lin, L et al. (2015) SLC transporters as therapeutic targets: emerging opportunities. Nat Rev Drug Discov 14: 543‐60 [PMID:27503090]Nalecz, KA. (2017) Solute Carriers in the Blood‐Brain Barier: Safety in Abundance. Neurochem Res 42: 795‐809 [PMID:27659854]Neul, C et al. (2016) Impact of Membrane Drug Transporters on Resistance to Small‐Molecule Tyrosine Kinase Inhibitors. Trends Pharmacol Sci 37: 904‐932 [PMID:25475361]Nigam, SK. (2015) What do drug transporters really do? Nat Rev Drug Discov 14: 29‐44 [PMID:26383868]Pedersen, NB et al. (2016) Glycosylation of solute carriers: mechanisms and functional consequences. Pflugers Arch 468: 159‐76 [PMID:27939446]Perland, E et al. (2017) Classification Systems of Secondary Active Transporters. Trends Pharmacol Sci 38: 305‐315 [PMID:28214518]Rives, ML et al. (2017) Potentiating SLC transporter activity: Emerging drug discovery opportunities. Biochem Pharmacol 135: 1‐11 8, 40, 301, 302, 432].The SLC1 family of sodium dependent transporters includes the plasma membrane located glutamate transporters and the neutral amino acid transporters ASCT1 and ASCT2 [225]. The crystal structure of a glutamate transporter homologue (GltPh) from Pyrococcus horikoshii supports this topology and indicates that the transporter assembles as a trimer, where each monomer is a functional unit capable of substrate permeation  reviewed by [281]). This structural data is in agreement with the proposed quaternary structure for EAAT2 [203] and several functional studies that propose the monomer is the functional unit . Recent evidence suggests that EAAT3 and EAAT4 may assemble as heterotrimers [402]. The activity of glutamate transporters located upon both neurones  and glia (predominantly EAAT 1 and 2) serves, dependent upon their location, to regulate excitatory neurotransmission, maintain low ambient extracellular concentrations of glutamate (protecting against excitotoxicity) and provide glutamate for metabolism including the glutamate‐glutamine cycle. The +/K+‐ATPaseNa that maintains the ion gradients that drive transport has been demonstrated to co‐assemble with EAAT1 and EAAT2 [453]. Recent evidence supports altered glutamate transport and novel roles in brain for splice variants of EAAT1 and EAAT2 . Three patients with dicarboxylic aminoaciduria (DA) were recently found to have loss‐of‐function mutations in EAAT3 [29]. DA is characterized by excessive excretion of the acidic amino acids glutamate and aspartate and EAAT3 is the predominant glutamate/aspartate transporter in the kidney. Enhanced expression of EAAT2 resulting from administration of β‐lactam antibiotics (e.g. ceftriaxone) is neuroprotective and occurs through NF‐κB‐mediated EAAT2 promoter activation  reviewed by [304]). γPPAR activation (e.g. by rosiglitazone) also leads to enhanced expression of EAAT though promoter activation [452]. In addition, several translational activators of EAAT2 have recently been described [108] along with treatments that increase the surface expression of EAAT2 , or prevent its down‐regulation (e.g. [216]). A thermodynamically uncoupled Cl‐ flux, activated by Na+ and glutamate  (Na+ and aspartate in the case of GltPh [458]), is sufficiently large, in the instances of EAAT4 and EAAT5, to influence neuronal excitability . Indeed, it has recently been suggested that the primary function of EAAT5 is as a slow anion channel gated by glutamate, rather than a glutamate transporter [192].Glutamate transporters present the unusual structural motif of 8TM segments and 2 re‐entrant loops . KB (or Ki) values derived in uptake assays are generally higher (e.g. [488]). In addition to acting as a poorly transportable inhibitor of EAAT2, ‐4‐methylglutamate, also known as SYM2081, is a competitive substrate for EAAT1  and additionally is a potent kainate receptor agonist [607] which renders the compound unsuitable for autoradiographic localisation of EAATs [19]. Similarly, at concentrations that inhibit EAAT2, dihydrokainate binds to kainate receptors [504]. WAY‐855 and WAY‐213613 are both non‐substrate inhibitors with a preference for EAAT2 over EAAT3 and EAAT1 . NBI‐59159 is a non‐substrate inhibitor with modest selectivity for EAAT3 over EAAT1 (>10‐fold) and EAAT2 (5‐fold) [142]. Analogously, L‐β‐threo‐benzyl‐aspartate (β‐BAL‐) is a competitive non‐substrate inhibitor that preferentially blocks EAAT3 versus EAAT1, or EAAT2 [162]. 3H]SYM2081[ demonstrates low affinity binding (KD≅ 6.0 μM) to EAAT1 and EAAT2 in rat brain homogenates [20] and EAAT1 in murine astrocyte membranes [18], whereas 3H]ETB‐TBOA[ binds with high affinity to all EAATs other than EAAT3 [489]. The novel isoxazole derivative (‐)‐HIP‐A may interact at the same site as TBOA and preferentially inhibit reverse transport of glutamate [107]. Threo‐3‐methylglutamate induces substrate‐like currents at EAAT4, but does not elicit heteroexchange of [3H]‐aspartate in synaptosome preparations, inconsistent with the behaviour of a substrate inhibitor [153]. Parawixin 1, a compound isolated from the venom from the spider Parawixia bistriata is a selective enhancer of the glutamate uptake through EAAT2 but not through EAAT1 or EAAT3 . In addition to the agents listed in the table, β‐hydroxyaspartateDL‐threo‐ and L‐trans‐2,4‐pyrolidine dicarboxylate act as non‐selective competitive substrate inhibitors of all EAATs. Zn2+ and arachidonic acid are putative endogenous modulators of EAATs with actions that differ across transporter subtypes (reviewed by [544]).The K(5‐fold) , 142. An+‐dependent exchange of small neutral amino acids such as Ala, Ser, Cys and Thr and their structure is predicted to be similar to that of the glutamate transporters . ASCT1 and ASCT2 also exhibit thermodynamically uncoupled chloride channel activity associated with substrate transport . Whereas EAATs counter‐transport K+ (see above) ASCTs do not and their function is independent of the intracellular concentration of K+[598].ASC transporters mediate NaL‐proline and trans‐4‐hydroxy‐proline[425]. At low pH ( ˜ 5.5) both ASCT1 and ASCT2 are able to exchange acidic amino acids such as L‐cysteate and glutamate . In addition to the inhibitors tabulated above, HgCl2, methylmercury and mersalyl, at low micromolar concentrations, non‐competitively inhibit ASCT2 by covalent modificiation of cysteine residues [412].The substrate specificity of ASCT1 may extend to [PMID:27233497]Bjorn‐Yoshimoto WE et al. (2016) The importance of the excitatory amino acid transporter 3 (EAAT3). Neurochem Int 98: 4‐18 [PMID:26687113]Fahlke C et al. (2016) Molecular physiology of EAAT anion channels . Pflugers Arch 468: 491‐502 [PMID:26096891]Fontana AC et al. (2015) Current approaches to enhance glutamate transporter function and expression. J Neurochem 134: 982‐1007 [PMID:24240778]Grewer C et al. (2014) SLC1 glutamate transporters. Pflugers Arch. 466: 3‐24 [PMID:25466154]Jensen AA et al. (2015) Excitatory amino acid transporters: recent insights into molecular mechanisms, novel modes of modulation and new therapeutic possibilities. Curr Opin Pharmacol 20: 116‐23 [PMID:23506861]Kanai Y et al. (2013) The SLC1 high‐affinity glutamate and neutral amino acid transporter family. Mol. Aspects Med. 34: 108‐20 [PMID:26033496]Takahashi K et al. (2015) Glutamate transporter EAAT2: regulation, function, and potential as a therapeutic target for neurological and psychiatric disease. Cell Mol Life Sci 72: 3489‐506 D‐glucose, D‐fructose, inositol (e.g. myo‐inositol) and related hexoses. Three classes of glucose transporter can be identified, separating GLUT1‐4 and 14, GLUT6, 8, 10 and 12; and GLUT5, 7, 9 and 11. Modelling suggests a 12 TM membrane topology, with intracellular termini, with functional transporters acting as homodimers or homotetramers.The SLC2 family transports D‐glucose, but not D‐fructose, in the direction of the concentration gradient and may be inhibited non‐selectively by phloretin and cytochalasin B. GLUT1 is the major glucose transporter in brain, placenta and erythrocytes, GLUT2 is found in the pancreas, liver and kidneys, GLUT3 is neuronal and placental, while GLUT4 is the insulin‐responsive transporter found in skeletal muscle, heart and adipose tissue. GLUT14 appears to result from gene duplication of GLUT3 and is expressed in the testes [577].Class I transporters are able to transport D‐fructose and appear to be insensitive to cytochalasin B. Class II transporters appear to be predominantly intracellularly located.Class II transporters transport phloretin and cytochalasin B[537].Proton‐coupled inositol transporters are expressed predominantly in the brain and can be inhibited by [PMID:20209635]Augustin R. (2010) The protein family of glucose transport facilitators: It's not only about glucose after all. IUBMB Life 62: 315‐33 [PMID:24598362]Klip A et al. (2014) Signal transduction meets vesicle traffic: the software and hardware of GLUT4 translocation. Am. J. Physiol., Cell Physiol. 306: C879‐86 [PMID:19389739]Leney SE et al. (2009) The molecular basis of insulin‐stimulated glucose uptake: signalling, trafficking and potential drug targets. J. Endocrinol. 203: 1‐18 [PMID:23506862]Mueckler M et al. (2013) The SLC2 (GLUT) family of membrane transporters. Mol. Aspects Med. 34: 121‐38 [PMID:12750891]Uldry M et al. (2004) The SLC2 family of facilitated hexose and polyol transporters. Pflugers Arch. 447: 480‐9 The SLC3 and SLC7 families combine to generate functional transporters, where the subunit composition is a disulphide‐linked combination of a heavy chain (SLC3 family) with a light chain (SLC7 family).SLC3 family members are single TM proteins with extensive glycosylation of the exterior C‐terminus, which heterodimerize with SLC7 family members in the endoplasmic reticulum and assist in the plasma membrane localization of the transporter.online database.Information on members of this family may be found in the SLC7 family members may be divided into two major groups: cationic amino acid transporters (CATs) and glycoprotein‐associated amino acid transporters (gpaATs).+), apparently as an exchange mechanism. These transporters are sensitive to inhibition by N‐ethylmaleimide.Cationic amino acid transporters are 14 TM proteins, which mediate pH‐ and sodium‐independent transport of cationic amino acids  amino acids independent of sodium and neutral  amino acids in a partially sodium‐dependent manner. These transporters are N‐ethylmaleimide‐insensitive. Heterodimers between rBAT and b0,+AT appear to mediate sodium‐independent system b0,+ transport of most of the neutral amino acids and cationic amino acids .Heterodimers between 4F2hc and yL‐alanine, L‐serine, L‐threonine, L‐glutamine and glycine), as well as D‐serine, in a sodium‐independent manner.Asc‐1 appears to heterodimerize with 4F2hc to allow the transport of small neutral amino acids  Amino Acid transporters in cancer and their relevance to "glutamine addiction": novel targets for the design of a new class of anticancer drugs. Cancer Res. 75: 1782‐8 [PMID:23506863]Fotiadis D et al. (2013) The SLC3 and SLC7 families of amino acid transporters. Mol. Aspects Med. 34: 139‐58 [PMID:14770309]Palacín M et al. (2004) The ancillary proteins of HATs: SLC3 family of amino acid transporters. Pflugers Arch. 447: 490‐4 [PMID:15772300]Palacín M et al. (2005) The genetics of heteromeric amino acid transporters. Physiology (Bethesda) 20: 112‐24 [PMID:14770310]Verrey F et al. (2004) CATs and HATs: the SLC7 family of amino acid transporters. Pflugers Arch. 447: 532‐42 3‐), but also carbonate and hydrogen sulphate (HSO4‐). SLC4 family members regulate bicarbonate fluxes as part of carbon dioxide movement, chyme neutralization and reabsorption in the kidney.Together with the SLC26 family, the SLC4 family of transporters subserve anion exchange, principally of chloride and bicarbonate , the electrogenic sodium‐dependent HCO3‐ transporters (NBCe1 and NBCe2) and the electroneutral HCO3‐ transporters (NBCn1 and NBCn2). Topographical information derives mainly from study of AE1, abundant in erythrocytes, which suggests a dimeric or tetrameric arrangement, with subunits made up of 13 TM domains and re‐entrant loops at TM9/10 and TM11/12. The N terminus exhibits sites for interaction with multiple proteins, including glycolytic enzymes, haemoglobin and cytoskeletal elements.Within the family, subgroups of transporters are identifiable: the electroneutral sodium‐independent Cl[PMID:27058983]Reithmeier RA et al. (2016) Band 3, the human red cell chloride/bicarbonate anion exchanger , in a structural context. Biochim Biophys Acta 1858: 1507‐32 +/substrate co‐transporters for glucose (e.g. choline), D‐glucose, monocarboxylates, myo‐inositol and I‐. Members of the SLC5 and SLC6 families, along with other unrelated Na+ cotransporters (i.e. Mhp1 and BetP), share a common structural core that contains an inverted repeat of 5TM α‐helical domains [2].The SLC5 family of sodium‐dependent glucose transporters includes, in mammals, the Naphlorizin, a natural dihydrocholine glucoside, that exhibits modest selectivity towards SGLT2 (see [573] for an extensive review). SGLT1 is predominantly expressed in the small intestine, mediating the absorption of glucose (e.g. D‐glucose), but also occurs in the brain, heart and in the late proximal straight tubule of the kidney. The expression of SGLT2 is almost exclusively restricted to the early proximal convoluted tubule of the kidney, where it is largely responsible for the renal reabsorption of glucose. SGLT3 is not a transporter but instead acts as a glucosensor generating an inwardly directed flux of Na+ that causes membrane depolarization [132].Detailed characterisation of members of the hexose transporter family is limited to SGLT1, 2 and 3, which are all inhibited in a competitive manner by 573] for a detailed quantification). Although SGLT1 and SGLT2 have been described as high‐ and low‐affinity sodium glucose co‐transporters, respectively, recent work suggests that they have a similar affinity for glucose under physiological conditions [258]. Selective blockers of SGLT2, and thus blocking ˜ 50% of renal glucose reabsorption, are in development for the treatment of diabetes (e.g. [84]).Recognition and transport of substrate by SGLTs requires that the sugar is a pyranose. De‐oxyglucose derivatives have reduced affinity for SGLT1, but the replacement of the sugar equatorial hydroxyl group by fluorine at some positions, excepting C2 and C3, is tolerated  proteins, (which are members of the SLC44 family) with weak Na+ dependence have been described [528].The high affinity, hemicholinium‐3‐sensitive, choline transporter (CHT) is expressed mainly in cholinergic neurones on nerve cell terminals and synaptic vesicles . In autonomic neurones, expression of CHT requires an activity‐dependent retrograde signal from postsynaptic neurones [iand KD values for hemicholinium‐3 listed in the table are for human CHT expressed in Xenopus laevis oocytes [411], or COS‐7 cells [17]. Hemicholinium mustard is a substrate for CHT that causes covalent modification and irreversible inactivation of the transporter. Several exogenous substances (e.g. triethylcholine) that are substrates for CHT act as precursors to cholinergic false transmitters.K‐ within thyrocytes. Transport of I‐ by NIS from the blood across the basolateral membrane followed by apical efflux into the colloidal lumen, mediated at least in part by pendrin (SLC22A4), and most likely not SMCT1 (SLC5A8) as once thought, provides the I‐ required for the synthesis of the thyroid hormones triiodothyronine (triiodothyronine) and thyroxine (4T) [49]. NIS is also expressed in the salivary glands, gastric mucosa, intestinal enterocytes and lactating breast. NIS mediates I‐ absorption in the intestine and I‐ secretion into the milk. SMVT is expressed on the apical membrane of intestinal enterocytes and colonocytes and is the main system responsible for biotin(vitamin H) and pantothenic acid (vitamin B5) uptake in humans [463]. SMVT located in kidney proximal tubule epithelial cells mediates the reabsorption of biotin and pantothenic acid. SMCT1 (SLC5A8), which transports a wide range of monocarboxylates, is expressed in the apical membrane of epithelia of the small intestine, colon, kidney, brain neurones and the retinal pigment epithelium [195]. SMCT2 (SLC5A12) also localises to the apical membrane of kidney, intestine, and colon, but in the brain and retina is restricted to astrocytes and Müller cells, respectively [195]. SMCT1 is a high‐affinity transporter whereas SMCT2 is a low‐affinity transporter. The physiological substrates for SMCT1 and SMCT2 are lactate (L‐lactic acid and D‐lactic acid), pyruvic acid, propanoic acid, and nicotinic acid in non‐colonic tissues such as the kidney. SMCT1 is also likely to be the principal transporter for the absorption of nicotinic acid (vitamin B3) in the intestine and kidney [214]. In the small intestine and colon, the physiological substrates for these transporters are nicotinic acid and the short‐chain fatty acids acetic acid, propanoic acid, and butyric acid that are produced by bacterial fermentation of dietary fiber [388]. In the kidney, SMCT2 is responsible for the bulk absorption of lactate because of its low‐affinity/high‐capacity nature. Absence of both transporters in the kidney leads to massive excretion of lactate in urine and consequently drastic decrease in the circulating levels of lactate in blood [521]. SMCT1 also functions as a tumour suppressor in the colon as well as in various other non‐colonic tissues [196]. The tumour‐suppressive function of SMCT1 is based on its ability to transport pyruvic acid, an inhibitor of histone deacetylases, into cells in non‐colonic tissues [522]; in the colon, the ability of SMCT1 to transport butyric acid and propanoic acid, also inhibitors of histone deacetylases, underlies the tumour‐suppressive function of this transporter . The ability of SMCT1 to promote histone acetylase inhibition through accumulation of butyric acid and propanoic acid in immune cells is also responsible for suppression of dendritic cell development in the colon [495].The sodium‐iodide symporter (NIS) is an iodide transporter found principally in the thyroid gland where it mediates the accumulation of I‐, 4‐ClO, thiocyanate and NO3‐ are competitive substrate inhibitors of NIS [141]. Lipoic acid appears to act as a competitive substrate inhibitor of SMVT [558] and the anticonvulsant drugs primidone and carbamazepine competitively block the transport of biotin by brush border vesicles prepared from human intestine [464].I+‐coupled SMIT1 and SMIT2 tabulated below and the third is proton‐coupled HMIT (SLC2A13). SMIT1 and SMIT2 have a widespread and overlapping tissue location but in polarized cells, such as the Madin‐Darby canine kidney cell line, they segregate to the basolateral and apical membranes, respectively [48]. In the nephron, SMIT1 mediates myo‐inositol uptake as a ‘compatible osmolyte’ when inner medullary tubules are exposed to increases in extracellular osmolality, whilst SMIT2 mediates the reabsorption of myo‐inositol from the filtrate. In some species  apically located SMIT2 is responsible for the uptake of myo‐inositol from the intestinal lumen [16].Three different mammalian myo‐inositol cotransporters are currently known; two are the NaD‐chiro‐inositol, but SMIT1 does not. In addition, whereas SMIT1 transports both D‐xylose and L‐xylose and D‐fucose and L‐fucose, SMIT2 transports only the D‐isomers of these sugars . Thus the substrate specificities of SMIT1 (for L‐fucose) and SMIT2 (for D‐chiro‐inositol) allow discrimination between the two SMITs. Human SMIT2 appears not to transport glucose [350].The data tabulated are those for dog SMIT1 and rabbit SMIT2. SMIT2 transports [PMID:27941935]DeFronzo RA et al. (2017) Renal, metabolic and cardiovascular considerations of SGLT2 inhibition. Nat Rev Nephrol 13: 11‐26 [PMID:27773781]Koepsell H. (2017) The Na+‐D‐glucose cotransporters SGLT1 and SGLT2 are targets for the treatment of diabetes and cancer. Pharmacol Ther 170 148‐165 [PMID:27012770]Lehmann A et al. (2016) Intestinal SGLT1 in metabolic health and disease. Am J Physiol Gastrointest Liver Physiol 310 G887‐98 [PMID:23506865]Wright EM. (2013) Glucose transport families SLC5 and SLC50. Mol. Aspects Med. 34: 183‐96 [PMID:21527736]Wright EM et al. (2011) Biology of human sodium glucose transporters. Physiol. Rev. 91: 733‐94 68, 89, 323] are primarily plasma membrane located and may be divided into four subfamilies that transport monoamines, GABA, glycine and neutral amino acids, plus the related bacterial NSS transporters [465]. The members of this superfamily share a structural motif of 10 TM segments that has been observed in crystal structures of the NSS bacterial homolog LeuTAa, a Na+‐dependent amino acid transporter from Aquiflex aeolicus [583] and in several other transporter families structurally related to LeuT [183].Members of the solute carrier family 6 (SLC6) of sodium‐ and (sometimes chloride‐) dependent neurotransmitter transporters RTI55[ labels all three monoamine transporters  with affinities between 0.5 and 5 nM. Cocaine is an inhibitor of all three transporters with pKi values between 6.5 and 7.2. Potential alternative splicing sites in non‐coding regions of SERT and NET have been identified. A bacterial homologue of SERT shows allosteric modulation by selected anti‐depressants [496].GABA are sufficient to sustain tonic inhibition mediated by high affinity GABAA receptors in certain neuronal populations [484]. GAT1 is the predominant GABA transporter in the brain and occurs primarily upon the terminals of presynaptic neurones and to a much lesser extent upon distal astocytic processes that are in proximity to axons terminals. GAT3 resides predominantly on distal astrocytic terminals that are close to the GABAergic synapse. By contrast, BGT1 occupies an extrasynaptic location possibly along with GAT2 which has limited expression in the brain [364]. TauT is a high affinity taurine transporter involved in osmotic balance that occurs in the brain and non‐neuronal tissues, such as the kidney, brush border membrane of the intestine and blood brain barrier . CT1, which transports creatine, has a ubiquitous expression pattern, often co‐localizing with creatine kinase [89].The activity of GABA‐transporters located predominantly upon neurones (GAT‐1), glia (GAT‐3) or both  serves to terminate phasic GABA‐ergic transmission, maintain low ambient extracellular concentrations of GABA, and recycle GABA for reuse by neurones. Nonetheless, ambient concentrations of 50 values for GAT1‐4 reported in the table reflect the range reported in the literature from studies of both human and mouse transporters. There is a tendency towards lower IC50 values for the human orthologue [327]. SNAP‐5114 is only weakly selective for GAT 2 and GAT3, with IC50 values in the range 22 to >30 μM at GAT1 and BGT1, whereas NNC052090 has at least an order of magnitude selectivity for BGT1  for reviews]. Compound (R)‐4d is a recently described compound that displays 20‐fold selectivity for GAT3 over GAT1 [190]. In addition to the inhibitors listed, deramciclane is a moderately potent, though non‐selective, inhibitor of all cloned GABA transporters . Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine that potently inhibit the uptake of 3H]GABA[ into rat synaptosomes have been described [309]. Several derivatives of exo‐THPO(e.g. N‐methyl‐exo‐THPO and N‐acetyloxyethyl‐exo‐THPO) demonstrate selectivity as blockers of astroglial, versus neuronal, uptake of GABA for reviews]. GAT3 is inhibited by physiologically relevant concentrations of Zn2+[106]. Taut transports GABA, but with low affinity, but CT1 does not, although it can be engineered to do so by mutagenesis guided by LeuT as a structural template [133]. Although inhibitors of creatine transport by CT1  are known (e.g. [114]) they insufficiently characterized to be included in the table.The IC42, 165, 211, 504] for reviews). GlyT1 transporter isoforms expressed in glia surrounding glutamatergic synapses regulate synaptic glycine concentrations influencing NMDA receptor‐mediated neurotransmission , but also are important, in early neonatal life, for regulating glycine concentrations at inhibitory glycinergic synapses [212]. Homozygous mice engineered to totally lack GlyT1 exhibit severe respiratory and motor deficiencies due to hyperactive glycinergic signalling and die within the first postnatal day . Disruption of GlyT1 restricted to forebrain neurones is associated with enhancement of EPSCs mediated by NMDA receptors and behaviours that are suggestive of a promnesic action [588]. GlyT2 transporters localised on the axons and boutons of glycinergic neurones appear crucial for efficient transmitter loading of synaptic vesicles but may not be essential for the termination of inhibitory neurotransmission . Mice in which GlyT2 has been deleted develop a fatal hyperekplexia phenotype during the second postnatal week [213] and mutations in the human gene encoding GlyT2 (SLC6A5) have been identified in patients with hyperekplexia (reviewed by [243]). ATB0+(SLC6A14) is a transporter for numerous dipolar and cationic amino acids and thus has a much broader substrate specificity than the glycine transporters alongside which it is grouped on the basis of structural similarity [89]. ATB0+ is expressed in various peripheral tissues [89]. By contrast PROT (SLC6A7), which is expressed only in brain in association with a subset of excitatory nerve terminals, shows specificity for the transport of L‐proline.Two gene products, GlyT1 and GlyT2, are known that give rise to transporters that are predominantly located on glia and neurones, respectively. Five variants of GlyT1  differing in their N‐ and C‐termini are generated by alternative promoter usage and splicing, and three splice variants of GlyT2  have also been identified  [546]. Inhibition of GLYT1 by the sarcosine derivatives NFPS, NPTS and Org 24598 is non‐competitive . IC50 values for Org 24598 reported in the literature vary, most likely due to differences in assay conditions . The tricyclic antidepressant amoxapine weakly inhibits GlyT2 (IC50 92 μM) with approximately 10‐fold selectivity over GlyT1 [406]. The endogenous lipids arachidonic acid and anandamide exert opposing effects upon GlyT1a, inhibiting (IC50˜ 2 μM) and potentiating (EC50˜ 13 μM) transport currents, respectively [421]. N‐arachidonyl‐glycine, γ‐aminobutyric acidN‐arachidonyl‐ and N‐arachidonyl‐D‐alanine have been described as endogenous non‐competitive inhibitors of GlyT2a, but not GlyT1b . Protons [25] and Zn2+[284] act as non‐competitive inhibitors of GlyT1b, with IC50 values of ˜ 100 nM and ˜ 10 μM respectively, but neither ion affects GlyT2 (reviewed by [544]). Glycine transport by GLYT1 is inhibited by +Li, whereas GLYT2 transport is stimulated (both in the presence of Na+) [433].0AT1 (SLC6A19), SLC6A17, SLC6A18, SLC6A20). Others may function as transporters for neurotransmitters or their precursors  [69].Certain members of neutral amino acid transport family are expressed upon the apical surface of epithelial cells and are important for the absorption of amino acids from the duodenum, jejunum and ileum and their reabsorption within the proximal tubule of the nephron  Kinase‐dependent Regulation of Monoamine Neurotransmitter Transporters. Pharmacol Rev 68: 888‐953 [PMID:22519513]Bröer S et al. (2012) The solute carrier 6 family of transporters. Br. J. Pharmacol. 167: 256‐78 [PMID:26542286]Joncquel‐Chevalier Curt M et al. (2015) Creatine biosynthesis and transport in health and disease. Biochimie 119: 146‐65 [PMID:27520881]Lohr KM et al. (2017) TMembrane transporters as mediators of synaptic dopamine dynamics: implications for disease. Eur J Neurosci 45: 20‐33 [PMID:23506866]Pramod AB et al. (2013) SLC6 transporters: structure, function, regulation, disease association and therapeutics. Mol. Aspects Med. 34: 197‐219 2+‐ATPase (PMCA) and sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase (SERCA), as well as the sodium/potassium/calcium exchangers , NCX allow recovery of intracellular calcium back to basal levels after cellular stimulation. When intracellular sodium ion levels rise, for example, following depolarisation, these transporters can operate in the reverse direction to allow calcium influx and sodium efflux, as an electrogenic mechanism. Structural modelling suggests the presence of 9 TM segments, with a large intracellular loop between the fifth and sixth TM segments.The sodium/calcium exchangers (NCX) use the extracellular sodium concentration to facilitate the extrusion of calcium out of the cell. Alongside the plasma membrane Ca3,4‐dichlorobenzamil and CBDMB act as non‐selective NCX inhibitors, while SEA0400, KB‐R7943, SN6, and ORM‐10103[283] act to inhibit NCX function with varying degrees of selectivity. BED is a selective NCX3 inhibitor [481] and and YM‐244769 inhibits NCX3 preferentially over other isoforms [277].Although subtype‐selective inhibitors of NCX function are not widely available, [PMID:23506867]Khananshvili D. (2013) The SLC8 gene family of sodium‐calcium exchangers (NCX) ‐ structure, function, and regulation in health and disease. Mol Aspects Med 34: 220‐35 [PMID:25998733]Sekler I (2015) Standing of giants shoulders the story of the mitochondrial Na(+)Ca(2+) exchanger. Biochem Biophys Res Commun 460: 50‐2 + (in) : 1 H+(out). Several isoforms, NHE6, NHE7, NHE8 and NHE9 appear to locate on intracellular membranes . Li+ and NH4+, but not K+, ions may also be transported by some isoforms. Modelling of the topology of these transporters indicates 12 TM regions with an extended intracellular C‐terminus containing multiple regulatory sites.Sodium/hydrogen exchangers or sodium/proton antiports are a family of transporters that maintain cellular pH by utilising the sodium gradient across the plasma membrane to extrude protons produced by metabolism, in a stoichiometry of 1 Na557] and osteoclasts [338]; gene disruption results in infertile male mice [557].NHE1 is considered to be a ubiquitously‐expressed ‘housekeeping’ transporter. NHE3 is highly expressed in the intestine and kidneys and regulate sodium movements in those tissues. NHE10 is present in sperm .Analogues of the non‐selective cation transport inhibitor amiloride appear to inhibit NHE function through competitive inhibition of the extracellular Na+/H+ exchangers. Mol. Aspects Med. 34: 236‐51 [PMID:23506868]Donowitz M et al. (2013) SLC9/NHE gene family, a plasma membrane and organellar family of Na[PMID:21054167]Kato A et al. (2011) Regulation of electroneutral NaCl absorption by the small intestine. Annu. Rev. Physiol. 73: 261‐81 [PMID:21171650]Ohgaki R et al. (2011) Organellar Na+/H+ exchangers: novel players in organelle pH regulation and their emerging functions. Biochemistry 50: 443‐50 [PMID:25680790]Parker MD et al. (2015) Na+‐H+ exchanger‐1 (NHE1) regulation in kidney proximal tubule. Cell. Mol. Life Sci. 72: 2061‐74 [PMID:24592239]Ruffin VA et al. (2014) Intracellular pH regulation by acid‐base transporters in mammalian neurons. Front Physiol 5: 43 α:OSTβ(SLC51), to maintain the enterohepatic circulation of bile acids . SLC10A6 (SOAT) functions as a sodium‐dependent transporter of sulphated solutes including sulfphated steroids and bile acids . Transport function has not yet been demonstrated for the 4 remaining members of the SLC10 family, SLC10A3 (P3), SLC10A4 (P4), SLC10A5 (P5), and SLC10A7 (P7), and the identity of their endogenous substrates remain unknown . Members of the SLC10 family are predicted to have seven transmembrane domains with an extracellular N‐terminus and cytoplasmic C‐terminus .The SLC10 family transport bile acids, sulphated solutes, and other xenobiotics in a sodium‐dependent manner. The founding members, SLC10A1 (NTCP) and SLC10A2 (ASBT) function, along with members of the ABC transporter family  and the organic solute transporter obligate heterodimer OST206] or SLC10A7 [210] failed to exhibit significant transport of taurocholic acid, pregnenolone sulphate, dehydroepiandrosterone sulphate or choline. SLC10A4 has recently been suggested to associate with neuronal vesicles [72].Heterologously expressed SLC10A4 [[PMID:24196564]Anwer MS et al. (2014) Sodium‐dependent bile salt transporters of the SLC10A transporter family: more than solute transporters. Pflugers Arch. 466: 77‐89 [PMID:23506869]Claro da Silva T et al. (2013) The solute carrier family 10 (SLC10): beyond bile acid transport. Mol. Aspects Med. 34: 252‐69 [PMID:28249269]Dawson PA et al. (2017) Roles of Ileal ASBT and OSTalpha‐OSTbeta in Regulating Bile. Dig Dis 35: 261‐266 [PMID:23603607]Zwicker BL et al. (2013) Transport and biological activities of bile acids. Int. J. Biochem. Cell Biol. 45: 1389‐98 The family of proton‐coupled metal ion transporters are responsible for movements of divalent cations, particularly ferrous and manganese ions, across the cell membrane (SLC11A2/DMT1) and across endosomal (SLC11A2/DMT1) or lysosomal/phagosomal membranes (SLC11A1/NRAMP1), dependent on proton transport. Both proteins appear to have 12 TM regions and cytoplasmic N‐ and C‐ termini. NRAMP1 is involved in antimicrobial action in macrophages, although its precise mechanism is undefined. Facilitated diffusion of divalent cations into phagosomes may increase intravesicular free radicals to damage the pathogen. Alternatively, export of divalent cations from the phagosome may deprive the pathogen of essential enzyme cofactors. SLC11A2/DMT1 is more widely expressed and appears to assist in divalent cation assimilation from the diet, as well as in phagocytotic cells.OMIM: 607948). Loss‐of‐function mutations in DMT1 are associated with microcytic anemia (OMIM: 206100).Loss‐of‐function mutations in NRAMP1 are associated with increased susceptibility to microbial infection  Iron entry in neurons and astrocytes: a link with synaptic activity. Front Mol Neurosci 8: 18 [PMID:23506870]Montalbetti N et al. (2013) Mammalian iron transporters: families SLC11 and SLC40. Mol. Aspects Med. 34: 270‐87 [PMID:26055722]Wessling‐Resnick M. (2015) Nramp1 and Other Transporters Involved in Metal Withholding during Infection. J. Biol. Chem. 290: 18984‐90 [PMID:22115751]Zheng W et al. (2012) Regulation of brain iron and copper homeostasis by brain barrier systems: implication in neurodegenerative diseases. Pharmacol. Ther. 133: 177‐88 The SLC12 family of chloride transporters contribute to ion fluxes across a variety of tissues, particularly in the kidney and choroid plexus of the brain. Within this family, further subfamilies are identifiable: NKCC1, NKCC2 and NCC constitute a group of therapeutically‐relevant transporters, targets for loop and thiazide diuretics. These 12 TM proteins exhibit cytoplasmic termini and an extended extracellular loop at TM7/8 and are kidney‐specific (NKCC2 and NCC) or show a more widespread distribution (NKCC1). A second family, the K‐Cl co‐transporters are also 12 TM domain proteins with cytoplasmic termini, but with an extended extracellular loop at TM 5/6. CCC6 exhibits structural similarities with the K‐Cl co‐transporters, while CCC9 is divergent, with 11 TM domains and a cytoplasmic N‐terminus and extracellular C‐terminus.DIOA is able to differentiate KCC isoforms from NKCC and NCC transporters, but also inhibits CFTR [275].[PMID:23506871]Arroyo JP et al. (2013) The SLC12 family of electroneutral cation‐coupled chloride cotransporters. Mol. Aspects Med. 34: 288‐98 [PMID:28577072]Bachmann S et al. (2017) Regulation of renal Na‐(K)‐Cl cotransporters by vasopressin. Pflugers Arch [PMID:27097893]Bazua‐Valenti S et al. (2016) Physiological role of SLC12 family members in the kidney. Am J Physiol Renal Physiol 311 F131‐44 [PMID:26911852]Huang X et al. (2016) Everything we always wanted to know about furosemide but were afraid to ask. Am J Physiol Renal Physiol 310: F958‐71 [PMID:26142773]Kahle KT et al. (2015) K‐Cl cotransporters, cell volume homeostasis, and neurological disease. Trends Mol Med [PMID:27861901]Martin‐Aragon Baudel MA et al. (2017) Chloride co‐transporters as possible therapeutic targets for stroke. J Neurochem 140: 195‐209 Within the SLC13 family, two groups of transporters may be differentiated on the basis of the substrates transported: NaS1 and NaS2 convey sulphate, while NaC1‐3 transport carboxylates. NaS1 and NaS2 transporters are made up of 13 TM domains, with an intracellular N terminus and are electrogenic with physiological roles in the intestine, kidney and placenta. NaC1, NaC2 and NaC3 are made up of 11 TM domains with an intracellular N terminus and are electrogenic, with physiological roles in the kidney and liver.[PMID:23506872]Bergeron MJ et al. (2013) SLC13 family of Na(+)‐coupled di‐ and tri‐carboxylate/sulfate transporters. Mol Aspects Med 34: 299‐312 [PMID:24193406]Markovich D. (2014) Na+‐sulfate cotransporter SLC13A1. Pflugers Arch. 466: 131‐7 [PMID:24114175]Pajor AM. (2014) Sodium‐coupled dicarboxylate and citrate transporters from the SLC13 family. Pflugers Arch. 466: 119‐30 urea movement down its concentration gradient. Multiple splice variants of these transporters have been identified; for UT‐A transporters, in particular, there is evidence for cell‐specific expression of these variants with functional impact [500]. Topographical modelling suggests that the majority of the variants of SLC14 transporters have 10 TM domains, with a glycosylated extracellular loop at TM5/6, and intracellular C‐ and N‐termini. The UT‐A1 splice variant, exceptionally, has 20 TM domains, equivalent to a combination of the UT‐A2 and UT‐A3 splice variants.As a product of protein catabolism, urea is moved around the body and through the kidneys for excretion. Although there is experimental evidence for concentrative urea transporters, these have not been defined at the molecular level. The SLC14 family are facilitative transporters, allowing [PMID:25488859]Esteva‐Font C et al. (2015) Urea transporter proteins as targets for small‐molecule diuretics. Nat Rev Nephrol 11: 113‐23 [PMID:26085670]LeMoine CM et al. (2015) Evolution of urea transporters in vertebrates: adaptation to urea's multiple roles and metabolic sources. J. Exp. Biol. 218: 1936‐1945 [PMID:23364530]Pannabecker TL. (2013) Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304: R488‐503 [PMID:23506873]Shayakul C et al. (2013) The urea transporter family (SLC14): physiological, pathological and structural aspects. Mol. Aspects Med. 34: 313‐22 [PMID:21449978]Stewart G. (2011) The emerging physiological roles of the SLC14A family of urea transporters. Br. J. Pharmacol. 164: 1780‐92 +‐coupled oligopeptide cotransporter family, is a group of membrane transporters known for their key role in the cellular uptake of di‐ and tripeptides (di/tripeptides). Of its members, SLC15A1 (PEPT1) chiefly mediates intestinal absorption of luminal di/tripeptides from dietary protein digestion, SLC15A2 (PEPT2) mainly allows renal tubular reuptake of di/tripeptides from ultrafiltration and brain‐to‐blood efflux of di/tripeptides in the choroid plexus, SLC15A3 (PHT2) and SLC15A4 (PHT1) interact with both di/tripeptides and histidine, e.g. in certain immune cells, and SLC15A5 has unknown physiological function. In addition, the SLC15 family of peptide transporters variably interacts with a very large number of peptidomimetics and peptide‐like drugs. It is conceivable, based on the currently acknowledged structural and functional differences, to divide the SLC15 family of peptide transporters into two subfamilies.The Solute Carrier 15 (SLC15) family of peptide transporters, alias Hcefadroxil, valacyclovir, 5‐aminolevulinic acid, L‐Dopa prodrugs, gemcitabine prodrugs, floxuridine prodrugs, Maillard reaction products, JBP485, zanamivir and oseltamivir prodrugs, and didanosine prodrugs.The members of the SLC15 family of peptide transporters are particularly promiscuous in the transport of di/tripeptides, and D‐amino acid containing peptides are also transported. While SLC15A3 and SLC15A4 transport histidine, none of them transport tetrapeptides. In addition, many molecules, among which beta‐lactam antibiotics, angiotensin‐converting enzyme inhibitors and sartans, variably interact with the SLC15 family transporters. Known substrates include SLC15A5, but to date there is no established biological function or reported pharmacology for this protein [498].There is evidence to suggest the existence of a fifth member of this transporter family, [PMID:23506874]Smith DE et al. (2013) Proton‐coupled oligopeptide transporter family SLC15: physiological, pharmacological and pathological implications. Mol. Aspects Med. 34: 323‐36 L‐lactic acid), pyruvic acid and ketone bodies, as well as aromatic amino acids. Topology modelling suggests 12 TM domains, with intracellular termini and an extended loop at TM 6/7.Members of the SLC16 family may be divided into subfamilies on the basis of substrate selectivities, particularly lactate (e.g. L‐lactic acid) and pyruvic acid.The proton‐coupled monocarboxylate transporters  allow transport of the products of cellular metabolism, principally lactate  Thyroid hormone transporters‐functions and clinical implications. Nat Rev Endocrinol 11: 406‐417 [PMID:27351344]Jones RS. (2016) Monocarboxylate Transporters: Therapeutic Targets and Prognostic Factors in Disease. Clin Pharmacol Ther 100: 454‐463 [PMID:23506875]Halestrap AP. (2013) The SLC16 gene family ‐ structure, role and regulation in health and disease. Mol Aspects Med 34: 337‐49 SLC34 family) and Type III (SLC20 family) transporters. Within the SLC17 family, however, further subgroups of organic anion transporters may be defined, allowing the accumulation of sialic acid in the endoplasmic reticulum and glutamate (e.g. L‐glutamic acid) or nucleotides in synaptic and secretory vesicles. Topology modelling suggests 12 TM domains.The SLC17 family are sometimes referred to as Type I sodium‐phosphate co‐transporters, alongside Type II , an autosomal recessive neurodegenerative disorder associated with sialic acid storage disease [551].Loss‐of‐function mutations in sialin are associated with Salla disease (39].Vesicular glutamate transporters (VGLUTs) allow accumulation of glutamate into synaptic vesicles, as well as secretory vesicles in endocrine tissues. The roles of VGLUTs in kidney and liver are unclear. These transporters appear to utilize the proton gradient and also express a chloride conductance [285].Endogenous ketoacids produced during fasting have been proposed to regulate VGLUT function through blocking chloride ion‐mediated allosteric enhancement of transporter function .The vesicular nucleotide transporter is the most recent member of the SLC17 family to have an assigned function. Uptake of DIDS and evans blue dye.VGLUTs and VNUT can be inhibited by [PMID:28616712]Moriyama Y et al. (2017) Vesicular nucleotide transporter (VNUT): appearance of an actress on the stage of purinergic signaling. Purinergic Signal [PMID:26514205]Omote H et al. (2016) Structure, Function, and Drug Interactions of Neurotransmitter Transporters in the Postgenomic Era. Annu Rev Pharmacol Toxicol 56: 385‐402 [PMID:23506876]Reimer RJ. (2013) SLC17: a functionally diverse family of organic anion transporters. Mol. Aspects Med. 34: 350‐9 [PMID:26577586]Takamori S. (2016) Vesicular glutamate transporters as anion channels? Pflugers Arch 468 513‐8 vacuolar ATPase that acidifies secretory vesicles (reviewed by [151]). The vesicular acetylcholine transporter  localizes to cholinergic neurons, but non‐neuronal expression has also been claimed [476]. Vesicular monoamine transporter 1  is mainly expressed in peripheral neuroendocrine cells, but most likely not in the CNS, whereas VMAT2 [159] distributes between both central and peripheral sympathetic monoaminergic neurones [152]. The vescular polyamine transporter (VPAT) is highly expressed in the lungs and placenta, with moderate expression in brain and testis, and with low expression in heart and skeletal muscle [250]. VPAT mediates vesicular accumulation of polyamines in mast cells [510].The vesicular amine transporters (VATs) are putative 12 TM domain proteins that function to transport singly positively charged amine neurotransmitters and hormones from the cytoplasm and concentrate them within secretory vesicles. They function as amine/proton antiporters driven by secondary active transport utilizing the proton gradient established by a multi‐subunit i values for endogenous and synthetic substrate inhibitors of human VMAT1 and VMAT2 are for inhibition of 3H]5‐HT[ uptake in transfected and permeabilised CV‐1 cells as detailed by [159]. In addition to the monoamines listed in the table, the trace amines tyramine and β‐phenylethylamine are probable substrates for VMAT2 [152]. Probes listed in the table are those currently employed; additional agents have been synthesized (e.g. [611]).pK[PMID:26408528]German CL et al. (2015) Regulation of the Dopamine and Vesicular Monoamine Transporters: Pharmacological Targets and Implications for Disease. Pharmacol Rev 67: 1005‐24 [PMID:23506877]Lawal HO et al. (2013) SLC18: Vesicular neurotransmitter transporters for monoamines and acetylcholine. Mol. Aspects Med. 34: 360‐72 [PMID:27520881]Lohr KM et al. (2017) Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease. Eur J Neurosci 45: 20‐33 [PMID:26514205]Omote H et al. (2016) Structure, Function, and Drug Interactions of Neurotransmitter Transporters in the Postgenomic Era. Annu Rev Pharmacol Toxicol 56: 385‐402 [PMID:25542076]Sitte HH et al. (2015) Amphetamines, new psychoactive drugs and the monoamine transporter cycle. Trends Pharmacol Sci 36: 41‐50 [PMID:20135628]Wimalasena K. (2011) Vesicular monoamine transporters: structure‐function, pharmacology, and medicinal chemistry. Med Res Rev 31: 483‐519 folic acid and thiamine are transported across the cell membrane, particularly in the intestine, kidneys and placenta, using pH differences as driving forces. Topological modelling suggests the transporters have 12 TM domains.The B vitamins 130].Loss‐of‐function mutations in ThTr1 underlie thiamine‐responsive megaloblastic anemia syndrome [[PMID:24396145]Matherly LH et al. (2014) The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer. Drug Metab. Dispos. 42: 632‐49 [PMID:23506878]Zhao R et al. (2013) Folate and thiamine transporters mediated by facilitative carriers (SLC19A1‐3 and SLC46A1) and folate receptors. Mol. Aspects Med. 34: 373‐85 SLC17 family) and Type II (SLC34 family). PiTs are cell‐surface transporters, composed of ten TM domains with extracellular C‐ and N‐termini. PiT1 is a focus for dietary phosphate and vitamin D regulation of parathyroid hormone secretion from the parathyroid gland. PiT2 appears to be involved in intestinal absorption of dietary phosphate.The SLC20 family is looked upon not only as ion transporters, but also as retroviral receptors. As ion transporters, they are sometimes referred to as Type III sodium‐phosphate co‐transporters, alongside Type I  Phosphate transporters and their function. Annu. Rev. Physiol. 75: 535‐50 [PMID:23506879]Forster IC et al. (2013) Phosphate transporters of the SLC20 and SLC34 families. Mol. Aspects Med. 34: 386‐95 [PMID:23506202]Shobeiri N et al. (2013) Phosphate: an old bone molecule but new cardiovascular risk factor. Br J Clin Pharmacol The SLC22 family of transporters is mostly composed of non‐selective transporters, which are expressed highly in liver, kidney and intestine, playing a major role in drug disposition. The family may be divided into three subfamilies based on the nature of the substrate transported: organic cations (OCTs), organic anions (OATs) and organic zwiterrion/cations (OCTN). Membrane topology is predicted to contain 12 TM domains with intracellular termini, and an extended extracellular loop at TM 1/2.+‐independent and reversible.Organic cation transporters (OCT) are electrogenic, Nacorticosterone and quinine are able to inhibit all three organic cation transporters.[PMID:21193033]A‐González N et al. (2011) Liver X receptors as regulators of macrophage inflammatory and metabolic pathways. Biochim. Biophys. Acta 1812: 982‐94 [PMID:23506881]Koepsell H. (2013) The SLC22 family with transporters of organic cations, anions and zwitterions. Mol. Aspects Med. 34: 413‐35 [PMID:23984399]Lozano E et al. (2013) Role of the plasma membrane transporter of organic cations OCT1 and its genetic variants in modern liver pharmacology. Biomed Res Int 2013: 692071 [PMID:24745985]Pelis RM et al. (2014) SLC22, SLC44, and SLC47 transporters–organic anion and cation transporters: molecular and cellular properties. Curr Top Membr 73: 233‐61 [PMID:27709005]Yin J et al. (2016) Renal drug transporters and their significance in drug‐drug interactions. Acta Pharm Sin B 6: 363‐373 L‐carnitine co‐transporters.Organic zwitterions/cation transporters (OCTN) function as organic cation uniporters, organic cation/proton exchangers or sodium/[PMID:23771822]Pochini L et al. (2013) OCTN cation transporters in health and disease: role as drug targets and assay development. J Biomol Screen 18: 851‐67 [PMID:22952014]Tamai I. (2013) Pharmacological and pathophysiological roles of carnitine/organic cation transporters . Biopharm Drug Dispos 34: 29‐44 [PMID:27709005]Yin J et al. (2016) Renal drug transporters and their significance in drug‐drug interactions. Acta Pharm Sin B 6: 363‐373 Organic anion transporters (OATs) are non‐selective transporters prominent in the kidney and intestine[PMID:23506881]Koepsell H. (2013) The SLC22 family with transporters of organic cations, anions and zwitterions. Mol. Aspects Med. 34: 413‐35 [PMID:27709005]Yin J et al. (2016) Renal drug transporters and their significance in drug‐drug interactions. Acta Pharm Sin B 6: 363‐373 [PMID:22841915]Burckhardt G. (2012) Drug transport by Organic Anion Transporters (OATs). Pharmacol. Ther. 136: 106‐30 [PMID:23506881]Koepsell H. (2013) The SLC22 family with transporters of organic cations, anions and zwitterions. Mol. Aspects Med. 34: 413‐35 [PMID:23686349]König J et al. (2013) Transporters and drug‐drug interactions: important determinants of drug disposition and effects. Pharmacol. Rev. 65: 944‐66 [PMID:23435786]Motohashi H et al. (2013) Organic cation transporter OCTs (SLC22) and MATEs (SLC47) in the human kidney. AAPS J 15: 581‐8 SLC2 family . Phloretin is considered a non‐selective inhibitor of these transporters, with an affinity in the micromolar range.Predicted to be 12 TM segment proteins, members of this family transport the reduced form of ascorbic acid  The sodium‐dependent ascorbic acid transporter family SLC23. Mol. Aspects Med. 34: 436‐54 [PMID:21418192]May JM. (2011) The SLC23 family of ascorbate transporters: ensuring that you get and keep your daily dose of vitamin C. Br. J. Pharmacol. 164: 1793‐801 SLC8A family), NKCX transporters are thought to be bidirectional, with the possibility of calcium influx following depolarization of the plasma membrane. Topological modeling suggests the presence of 10 TM domains, with a large intracellular loop between the fifth and sixth TM regions.The sodium/potassium/calcium exchange family of transporters utilize the extracellular sodium gradient to drive calcium and potassium co‐transport out of the cell. As is the case for NCX transporters  The SLC24 gene family of Na+‐dependent Na+‐Ca2+ exchangers: structure‐function relationships. Curr Top Membr 73: 263‐87 [PMID:24745986]Schnetkamp PP et al. (2014) The SLC24 family of K[PMID:25998733]Sekler I. (2015) Standing of giants shoulders the story of the mitochondrial Na(+)Ca(2+) exchanger. Biochem. Biophys. Res. Commun. 460: 50‐2 Mitochondrial transporters are nuclear‐encoded proteins, which convey solutes across the inner mitochondrial membrane. Topological modelling suggests homodimeric transporters, each with six TM segments and termini in the cytosol.citric acid export from the mitochondria to allow the generation of oxalacetic acid and acetyl CoA through the action of ATP:citrate lyase.Mitochondrial di‐ and tri‐carboxylic acid transporters are grouped on the basis of commonality of substrates and include the citrate transporter which facilitates urea cycle by exchanging cytosolic ornithine (L‐ornithine and D‐ornithine) for mitochondrial citrulline (L‐citrulline and D‐citrulline) in equimolar amounts. Further members of the family include transporters of S‐adenosylmethionine and carnitine.Mitochondrial amino acid transporters can be subdivided on the basis of their substrates. Mitochondrial ornithine transporters play a role in the spermine[178]. Loss‐of‐function mutations in these genes are associated with hyperornithinemia‐hyperammonemia‐homocitrulli‐ nuria.Both ornithine transporters are inhibited by the polyamine ATP production.Mitochondrial phosphate transporters allow the import of inorganic phosphate for ADP for mitochondrial ATP. Further members of the mitochondrial nucleotide transporter subfamily convey diverse substrates including CoA, although not all members have had substrates identified.Mitochondrial nucleotide transporters, defined by structural similarlities, include the adenine nucleotide translocator family , which under conditions of aerobic metabolism, allow coupling between mitochondrial oxidative phosphorylation and cytosolic energy consumption by exchanging cytosolic Mitochondrial uncoupling proteins allow dissipation of the mitochondrial proton gradient associated with thermogenesis and regulation of radical formation.Many of the transporters identified below have yet to be assigned functions and are currently regarded as orphans.online database.Information on members of this family may be found in the [PMID:28088333]Baffy G. (2017) Mitochondrial uncoupling in cancer cells: Liabilities and opportunities. Biochim Biophys Acta 1858: 655‐664 [PMID:27984203]Bertholet, AM et al. (2017) UCP1: A transporter for H+ and fatty acid anions. Biochimie 134: 28‐34 [PMID:23506884]Clémençon B et al. (2013) The mitochondrial ADP/ATP carrier (SLC25 family): pathological implications of its dysfunction. Mol. Aspects Med. 34: 485‐93 [PMID:23266187]Palmieri F. (2013) The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol. Aspects Med. 34: 465‐84 [PMID:26091567]Seifert EL et al. (2015) The mitochondrial phosphate carrier: Role in oxidative metabolism, calcium handling and mitochondrial disease. Biochem. Biophys. Res. Commun. 464: 369‐75 [PMID:28522206]Taylor, EB. (2017) Functional Properties of the Mitochondrial Carrier System. Trends Cell Biol Along with the SLC4 family, the SLC26 family acts to allow movement of monovalent and divalent anions across cell membranes. The predicted topology is of 10‐14 TM domains with intracellular C‐ and N‐termini, probably existing as dimers. Within the family, subgroups may be identified on the basis of functional differences, which appear to function as anion exchangers and anion channels (SLC26A7 and SLC26A9).[PMID:23506885]Alper SL et al. (2013) The SLC26 gene family of anion transporters and channels. Mol. Aspects Med. 34: 494‐515 [PMID:21054167]Kato A et al. (2011) Regulation of electroneutral NaCl absorption by the small intestine. Annu. Rev. Physiol. 73: 261‐81 [PMID:22116372]Nofziger C et al. (2011) Pendrin function in airway epithelia. Cell. Physiol. Biochem. 28: 571‐8 [PMID:23636174]Soleimani M. (2013) SLC26 Cl(‐)/HCO3(‐) exchangers in the kidney: roles in health and disease. Kidney Int. 343, 475], transmembrane segments, and are predicted on the basis of structural similarities to form dimers. SLC27 members have several structural domains: integral membrane associated domain, peripheral membrane associated domain, FATP signature, intracellular AMP binding motif, dimerization domain, lipocalin motif, and an ER localization domain (identified in FATP4 only) . These transporters are unusual in that they appear to express intrinsic very long‐chain acyl‐CoA synthetase  enzyme activity. Within the cell, these transporters may associate with plasma and peroxisomal membranes. FATP1‐4 and ‐6 transport long‐ and very long‐chain fatty acids, while FATP5 transports long‐chain fatty acids as well as bile acids .Fatty acid transporter proteins (FATPs) are a family (SLC27) of six transporters (FATP1‐6). They have at least one, and possibly six  and FATP4 , as well as bile acid inhibitors of FATP5 [609], have been described; analysis of the mechanism of action of some of these inhibitors suggests that transport may be selectively inhibited without altering enzymatic activity of the FATP.Although the stoichiometry of fatty acid transport is unclear, it has been proposed to be facilitated by the coupling of fatty acid transport to conjugation with C1‐BODIPY‐C12 accumulation has been used as a non‐selective index of fatty acid transporter activity.FATP2 has two variants: Variant 1 encodes the full‐length protein, while Variant 2 encodes a shorter isoform missing an internal protein segment. FATP6 also has two variants: Variant 2 encodes the same protein as Variant 1 but has an additional segment in the 5' UTR.[PMID:23506886]Anderson CM et al. (2013) SLC27 fatty acid transport proteins. Mol. Aspects Med. 34: 516‐28 [PMID:26416577]Dourlen P et al. (2015) Fatty acid transport proteins in disease: New insights from invertebrate models. Prog Lipid Res 60: 30‐40 [PMID:20206486]Schwenk RW et al. (2010) Fatty acid transport across the cell membrane: regulation by fatty acid transporters. Prostaglandins Leukot. Essent. Fatty Acids 82: 149‐54 Nucleoside transporters are divided into two families, the sodium‐dependent, concentrative solute carrier family 28 (SLC28) and the equilibrative, solute carrier family 29 (SLC29). The endogenous substrates are typically nucleosides, although some family members can also transport nucleobases and organic cations.SLC28 family membersappear to have 13 TM segments with cytoplasmic N‐termini and extracellular C‐termini, and function as concentrative nucleoside transporters.+‐dependent (stoichiometry 1 Na+: 1 nucleoside (in)) nucleoside transporters have been defined on the basis of substrate and inhibitor selectivity: CNT4  and CNT5 .A further two Na32]. ENT1‐3 are described as broad‐spectrum equilibrative nucleoside transporters, while ENT4 is primarily a polyspecific organic cation transporter at neutral pH [252]. ENT4 transports adenosine only under acidotic conditions [36].SLC29 family members appear to be composed of 11 TM segments with cytoplasmic N‐termini and extracellular C‐termini. ENT1, ENT2 and ENT4 are cell‐surface transporters, while ENT3 is intracellular, possibly lysosomal [[PMID:27759477]Boswell‐Casteel RC et al. (2017) Equilibrative nucleoside transporters‐A review. Nucleosides Nucleotides Nucleic Acids 36: 7‐30 [PMID:25713533]Pastor‐Anglada M et al. (2015) Nucleoside transporter proteins as biomarkers of drug responsiveness and drug targets. Front Pharmacol 6: 13 [PMID:23506887]Young JD et al. (2013) The human concentrative and equilibrative nucleoside transporter families, SLC28 and SLC29. Mol. Aspects Med. 34: 529‐47 [PMID:27284054]Young JD. (2016) The SLC28 (CNT) and SLC29 (ENT) nucleoside transporter families: a 30‐year collaborative odyssey. Biochem Soc Trans 44: 869‐76 SLC39 family, SLC30 transporters regulate the movement of zinc ions around the cell. In particular, these transporters remove zinc ions from the cytosol, allowing accumulation into intracellular compartments or efflux through the plasma membrane. ZnT1 is thought to be placed on the plasma membrane extruding zinc, while ZnT3 is associated with synaptic vesicles and ZnT4 and ZnT5 are linked with secretory granules. Membrane topology predictions suggest a multimeric assembly, potentially heteromultimeric [506], with subunits having six TM domains, and both termini being cytoplasmic. Dityrosine covalent linking has been suggested as a mechanism for dimerisation, particularly for ZnT3 [469]. The mechanism for zinc transport is unknown.Along with the online database.Information on members of this family may be found in the ZnT8/SLC30A8 is described as a type 1 diabetes susceptibility gene.Zinc fluxes may be monitored through the use of radioisotopic Zn‐65 or the fluorescent dye FluoZin 3.[PMID:23719866]Bouron A et al. (2013) Contribution of calcium‐conducting channels to the transport of zinc ions. Pflugers Arch. [PMID:27394923]Hojyo S et al. (2016) Zinc transporters and signaling in physiology and pathogenesis. Arch Biochem Biophys 611: 43‐50 [PMID:23506888]Huang L et al. (2013) The SLC30 family of zinc transporters ‐ a review of current understanding of their biological and pathophysiological roles. Mol. Aspects Med. 34: 548‐60 [PMID:24710731]Kambe T et al. (2014) Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell. Mol. Life Sci. 71: 3281‐95 [PMID:26084690]Kambe T et al. (2015) The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism. Physiol. Rev. 95: 749‐784 Cu‐ATPases are involved in the regulation of cellular copper levels. The CTR1 transporter is a cell‐surface transporter to allow monovalent copper accumulation into cells, while CTR2 appears to be a vacuolar/vesicular transporter [442]. Functional copper transporters appear to be trimeric with each subunit having three TM regions and an extracellular N‐terminus. CTR1 is considered to be a higher affinity copper transporter compared to CTR2. The stoichiometry of copper accumulation is unclear, but appears to be energy‐independent [334].SLC31 family members, alongside the 334].Copper accumulation through CTR1 is sensitive to silver ions, but not divalent cations [[PMID:20159940]Howell SB et al. (2010) Copper transporters and the cellular pharmacology of the platinum‐containing cancer drugs. Mol. Pharmacol. 77: 887‐94 [PMID:26745404]Kaplan JH et al. (2016) How Mammalian Cells Acquire Copper: An Essential but Potentially Toxic Metal. Biophys J 110: 7‐13 [PMID:23506889]Kim H et al. (2013) SLC31 (CTR) family of copper transporters in health and disease. Mol. Aspects Med. 34: 561‐70 [PMID:24745987]Monné M et al. (2014) Antiporters of the mitochondrial carrier family. Curr Top Membr 73: 289‐320 GABA, or glycine, into synaptic vesicles , and is a member of the structurally‐defined amino acid‐polyamine‐organocation/APC clan composed of SLC32, SLC36 and SLC38 transporter families (see [477]). VIAAT was originally suggested to be composed of 10 TM segments with cytoplasmic N‐ and C‐termini [372]. However, an alternative 9TM structure with the N terminus facing the cytoplasm and the C terminus residing in the synaptic vesicle lumen has subsequently been reported [369]. VIAAT acts as an antiporter for inhibitory amino acids and protons. The accumulation of GABA and glycine within vesicles is driven by both the chemical (ΔpH) and electrical (Δψ) components of the proton electrochemical gradient (ΔμH+) established by a vacuolar H+‐ATPase [372]. However, one study, [286], presented evidence that VIAAT is instead a Cl‐/GABA co‐transporter. VIAAT co‐exists with VGLUT1(SLC17A7), or VGLUT2(SLC17A6), in the synaptic vesicles of selected nerve terminals . VIAAT knock out mice die between embryonic day 18.5 and birth [570]. In cultures of spinal cord neurones established from earlier embryos, the co‐release of of GABA and glycine from synaptic vesicles is drastically reduced, providing direct evidence for the role of VIAAT in the sequestration of both transmitters .The vesicular inhibitory amino acid transporter, VIAAT , which is the sole representative of the SLC32 family, transports [PMID:24745982]Anne C et al. (2014) Vesicular neurotransmitter transporters: mechanistic aspects. Curr Top Membr 73: 149‐74 [PMID:23506890]Schiöth HB et al. (2013) Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol. Aspects Med. 34: 571‐85 acetyl CoA. SLC33A1/AT1 is a putative 11 TM transporter present on the endoplasmic reticulum, expressed in all tissues, but particularly abundant in the pancreas [293], which imports cytosolic acetyl CoA into these intracellular organelles.Acetylation of proteins is a post‐translational modification mediated by specific acetyltransferases, using the donor acetyl CoA transport through AT1 was inhibited by coenzyme A, but not acetic acid, ATP or UDP‐galactose[282]. A loss‐of‐function mutation in ACATN1/SLC33A1 has been associated with spastic paraplegia , although this observation could not be replicated in a subsequent study [478].In heterologous expression studies, [PMID:12739170]Hirabayashi Y et al. (2004) The acetyl‐CoA transporter family SLC33. Pflugers Arch. 447: 760‐2 [PMID:23506891]Hirabayashi Y et al. (2013) The acetyl‐CoA transporter family SLC33. Mol. Aspects Med. 34: 586‐9 SLC17 family) and Type III (SLC20 family) transporters. Topological modelling suggests eight TM domains with C‐ and N‐ termini in the cytoplasm, and a re‐entrant loop at TM7/8. SLC34 family members are expressed on the apical surfaces of epithelia in the intestine and kidneys to regulate body phosphate levels, principally NaPi‐IIa and NaPi‐IIb, respectively. NaPi‐IIa and NaPi‐IIb are electrogenic, while NaPiIIc is electroneutral [15].The SLC34 family are sometimes referred to as Type II sodium‐phosphate co‐transporters, alongside Type I  Phosphate transporters and their function. Annu. Rev. Physiol. 75: 535‐50 [PMID:23506879]Forster IC et al. (2013) Phosphate transporters of the SLC20 and SLC34 families. Mol. Aspects Med. 34: 386‐95 [PMID:23506202]Shobeiri N et al. (2013) Phosphate: an old bone molecule but new cardiovascular risk factor. Br J Clin Pharmacol [PMID:24352629]Wagner CA et al. (2014) The SLC34 family of sodium‐dependent phosphate transporters. Pflugers Arch. 466: 139‐53 Glycoprotein formation in the Golgi and endoplasmic reticulum relies on the accumulation of nucleotide‐conjugated sugars via the SLC35 family of transporters. These transporters have a predicted topology of 10 TM domains, with cytoplasmic termini, and function as exchangers, swopping nucleoside monophosphates for the corresponding nucleoside diphosphate conjugated sugar. Five subfamilies of transporters have been identified on the basis of sequence similarity, namely SLC35A1, SLC35A2, SLC35A3, SLC35A4 and SLC35A5; SLC35B1, SLC35B2, SLC35B3 and SLC35B4; SLC35C1 and SLC35C2; SLC35D1, SL35D1, SLC35D2 and SLC35D3, and the subfamily of orphan SLC35 transporters, SLC35E1‐4 and SLC35F1‐5.[PMID:12759756]Ishida N et al. (2004) Molecular physiology and pathology of the nucleotide sugar transporter family (SLC35). Pflugers Arch. 447: 768‐75 [PMID:27261257]Orellana A. (2016) Overview of Nucleotide Sugar Transporter Gene Family Functions Across Multiple Species. J Mol Biol 428: 3150‐65 [PMID:23506892]Song Z. (2013) Roles of the nucleotide sugar transporters (SLC35 family) in health and disease. Mol. Aspects Med. 34: 590‐600 5, 461]. PAT2 is expressed at the apical membrane of the renal proximal tubule [70] and at the plasma‐membrane in brown/beige adipocytes [539]. More comprehensive lists of substrates can be found within the reviews under Further Reading and in the references.Members of the SLC36 family of proton‐coupled amino acid transporters are involved in membrane transport of amino acids and derivatives. The four transporters show variable tissue expression patterns and are expressed in various cell types at the plasma‐membrane and in intracellular organelles. PAT1 is expressed at the luminal surface of the small intestine and absorbs amino acids and derivatives [3]. In lysosomes, PAT1 functions as an efflux mechanism for amino acids produced during intralysosomal proteolysis [[PMID:23506890]Schiöth HB et al. (2013) Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol. Aspects Med. 34: 571‐85 [PMID:21501141]Thwaites DT et al. (2011) The SLC36 family of proton‐coupled amino acid transporters and their potential role in drug transport. Br. J. Pharmacol. 164: 1802‐16 [PMID:17123464]Thwaites DT et al. (2007) Deciphering the mechanisms of intestinal imino (and amino) acid transport: the redemption of SLC36A1. Biochim. Biophys. Acta 1768: 179‐97 The family of sugar‐phosphate exchangers pass particular phosphorylated sugars across intracellular membranes, exchanging for inorganic phosphate. Of the family of sugar phosphate transporters, most information is available on SPX4, the glucose‐6‐phosphate transporter. This is a 10 TM domain protein with cytoplasmic termini and is associated with the endoplasmic reticulum, with tissue‐specific splice variation.[PMID:24745989]Chou JY et al. (2014) The SLC37 family of sugar‐phosphate/phosphate exchangers. Curr Top Membr 73: 357‐82 [PMID:23506893]Chou JY et al. (2013) The SLC37 family of phosphate‐linked sugar phosphate antiporters. Mol. Aspects Med. 34: 601‐11 477].The SLC38 family of transporters appears to be responsible for the functionally‐defined system A and system N mechanisms of amino acid transport and are mostly expressed in the CNS. Two distinct subfamilies are identifiable within the SLC38 transporters. SNAT1, SNAT2 and SNAT4 appear to resemble system A transporters in accumulating neutral amino acids under the influence of the sodium gradient. SNAT3 and SNAT5 appear to resemble system N transporters in utilizing proton co‐transport to accumulate amino acids. The predicted membrane topology is of 11 TM domains with an extracellular C‐terminus and intracellular N‐terminus [[PMID:26724577]Bhutia, YD et al. (2016) Glutamine transporters in mammalian cells and their functions in physiology and cancer. Biochim Biophys Acta 1863: 2531‐9 [PMID:24193407]Bröer S. (2014) The SLC38 family of sodium‐amino acid co‐transporters. Pflugers Arch. 466: 155‐72 [PMID:21568940]Bröer S et al. (2011) The role of amino acid transporters in inherited and acquired diseases. Biochem. J. 436: 193‐211 [PMID:21511949]Hägglund MG et al. (2011) Identification of SLC38A7 (SNAT7) protein as a glutamine transporter expressed in neurons. J. Biol. Chem. 286: 20500‐11 [PMID:23506890]Schiöth HB et al. (2013) Evolutionary origin of amino acid transporter families SLC32, SLC36 and SLC38 and physiological, pathological and therapeutic aspects. Mol. Aspects Med. 34: 571‐85 SLC30 family, SLC39 family members regulate zinc movement in cells. SLC39 metal ion transporters accumulate zinc into the cytosol. Membrane topology modelling suggests the presence of eight TM regions with both termini extracellular or in the lumen of intracellular organelles. The mechanism for zinc transport for many members is unknown but appears to involve co‐transport of bicarbonate ions .Along with the Zinc fluxes may be monitored through the use of radioisotopic Zn‐65 or the fluorescent dye FluoZin 3.DIDS has been reported to inhibit cation accumulation through ZIP14 [209].The bicarbonate transport inhibitor [PMID:27394923]Hojyo S et al. (2016) Zinc transporters and signaling in physiology and pathogenesis. Arch Biochem Biophys 611: 43‐50 [PMID:23506894]Jeong J et al. (2013) The SLC39 family of zinc transporters. Mol. Aspects Med. 34: 612‐9 [PMID:24710731]Kambe T et al. (2014) Current understanding of ZIP and ZnT zinc transporters in human health and diseases. Cell. Mol. Life Sci. 71: 3281‐95 [PMID:26084690]Kambe T et al. (2015) The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism. Physiol. Rev. 95: 749‐784 [PMID:25130547]Marger L et al. (2014) Zinc: an underappreciated modulatory factor of brain function. Biochem. Pharmacol. 91: 426‐35 SLC11 family of proton‐coupled metal transporters, ferroportin allows the accumulation of iron from the diet. Whilst SLC11A2 functions on the apical membrane, ferroportin acts on the basolateral side of the enterocyte, as well as regulating macrophage and placental iron levels. The predicted topology is of 12 TM domains, with intracellular termini [448], with the functional transporter potentially a dimeric arrangement . Ferroportin is essential for iron homeostasis [138]. Ferroportin is expressed on the surface of cells that store and transport iron, such as duodenal enterocytes, hepatocytes, adipocytes and reticuloendothelial macrophages. Levels of ferroportin are regulated by its association with (binding to) hepcidin, a 25 amino acid hormone responsive to circulating iron levels . Hepcidin binding targets ferroportin for internalisation and degradation, lowering the levels of iron export to the blood. Novel therapeutic agents which stabilise ferroportin or protect it from hepcidin‐induced degradation are being developed as anti‐anemia agents. Anti‐ferroportin monoclonal antibodies are such an agent.Alongside the HAMP, P81172), cleaved into hepcidin‐25 and hepcidin‐20, is a small protein that increases upon inflammation, binds to ferroportin to regulate its cellular distribution and degradation. Gene disruption in mice results in embryonic lethality [138], while loss‐of‐function mutations in man are associated with haemochromatosis [122].Hepcidin  The SLC40 basolateral iron transporter family (IREG1/ferroportin/MTP1). Pflugers Arch. 447: 801‐6 [PMID:23506870]Montalbetti N et al. (2013) Mammalian iron transporters: families SLC11 and SLC40. Mol. Aspects Med. 34: 270‐87 2+ efflux [317], possibly as a result of co‐expression of particular protein partners (see [462]). Topological modelling suggests 10 TM domains with cytoplasmic C‐ and N‐ termini.By analogy with bacterial orthologues, this family is probably magnesium transporters. The prokaryote orthologue, MgtE, is responsible for uptake of divalent cations, while the heterologous expression studies of mammalian proteins suggest Mg[PMID:23954807]Payandeh J et al. (2013) The structure and regulation of magnesium selective ion channels. Biochim. Biophys. Acta [PMID:23506895]Sahni J et al. (2013) The SLC41 family of MgtE‐like magnesium transporters. Mol. Aspects Med. 34: 620‐8 [PMID:24745990]Schweigel‐Röntgen M et al. (2014) SLC41 transporters–molecular identification and functional role. Curr Top Membr 73: 383‐410 RHCE (P18577) and RHD(Q02161), expressed on the surface of erythrocytes. On erythrocytes, RhAG associates with these antigens and functions as an ammonium transporter. RhBG and RhBG are non‐erythroid related sequences associated with epithelia. Topological modelling suggests the presence of 12TM with cytoplasmic N‐ and C‐ termini. The majority of information on these transporters derives from orthologues in yeast, plants and bacteria. More recent evidence points to family members being permeable to carbon dioxide, leading to the term gas channels.Rhesus is commonly defined as a ‘factor’ that determines, in part, blood type, and whether neonates suffer from haemolytic disease of the newborn. These glycoprotein antigens derive from two genes, [PMID:23506896]Nakhoul NL et al. (2013) Characteristics of mammalian Rh glycoproteins (SLC42 transporters) and their role in acid‐base transport. Mol. Aspects Med. 34: 629‐37 [PMID:21048022]Weiner ID et al. (2011) Role of NH3 and NH4+ transporters in renal acid‐base transport. Am. J. Physiol. Renal Physiol. 300: F11‐23 [PMID:24647713]Weiner ID et al. (2014) Ammonia transport in the kidney by Rhesus glycoproteins. Am. J. Physiol. Renal Physiol. 306: F1107‐20 SLC7 family. LAT3 and LAT4 contain 12 putative TM domains with both N and C termini located intracellularly. They transport neutral amino acids in a manner independent of Na+ and Cl‐ and with two kinetic components . LAT3/SLC43A1 is expressed in human tissues at high levels in the pancreas, liver, skeletal muscle and fetal liver [27] whereas LAT4/SLC43A2 is primarily expressed in the placenta, kidney and peripheral blood leukocytes [53]. SLC43A3 is expressed in vascular endothelial cells [555] but remains to be characterised.LAT3 (SLC43A1) and LAT4 (SLC43A2) are transporters with system L amino acid transporter activity, along with the structurally and functionally distinct transporters LAT1 and LAT2 that are members of the N‐ethylmaleimide inhibits its function [27] and at LAT4 inhibits the low‐, but not high‐affinity component of transport [53].Covalent modification of LAT3 by [PMID:23268354]Bodoy S et al. (2013) The small SLC43 family: facilitator system l amino acid transporters and the orphan EEG1. Mol. Aspects Med. 34: 638‐45 528]. CTL family members are putative 10TM domain proteins with extracellular termini that mediate Na+‐independent transport of choline with an affinity that is intermediate to that of the high affinity choline transporter CHT1 (SLC5A7) and the low affinity organic‐cation transporters [OCT1 (SLC22A1) and OCT2 (SLC22A2)] [380]. CLT1 is expressed almost ubiquitously in human tissues [568] and mediates choline transport across the plasma and mitochondrial membranes [379]. Transport of choline by CTL2, which in rodents is expressed as two isoforms  in lung, colon, inner ear and spleen and to a lesser extent in brain, tongue, liver, and kidney, has only recently been demonstrated . CTL3‐5 remain to be characterized functionally.Members of the choline transporter‐like family are encoded by five genes (CTL1‐CTL5) with further diversity occurring through alternative splicing of CTL1, 4 and 5 [265]; rat renal tubule epithelial cells [580]; human colon carcinoma cells [320]; human keratinocytes [536] and human neuroblastoma cells [581]. Choline uptake by CLT1 is inhibited by numerous organic cations . In the guinea‐pig, CTL2 is a target for antibody‐induced hearing loss [394] and in man, a polymorphism in CTL2 constitutes the human neutrophil alloantigen‐3a .Data tabulated are features observed for CLT1 endogenous to: rat astrocytes [[PMID:24532461]Inazu M. (2014) Choline transporter‐like proteins CTLs/SLC44 family as a novel molecular target for cancer therapy. Biopharm Drug Dispos 35: 431‐49 [PMID:23506897]Traiffort E et al. (2013) The choline transporter‐like family SLC44: properties and roles in human diseases. Mol. Aspects Med. 34: 646‐54 491]. The protein is predicted to have 12TM domains, with intracellular termini. The SLC45A2 gene is thought to encode a transporter protein that mediates melanin synthesis. Mutations in SLC45A2 are a cause of oculocutaneous albinism type 4 (e.g. [401]), and polymorphisms in this gene are associated with variations in skin and hair color (e.g. [219]).Members of the SLC45 family remain to be fully characterised. SLC45A1 was initially identified in the rat brain, particularly predominant in the hindbrain, as a proton‐associated sugar transport, induced by hypercapnia [[PMID:25164149]Bartölke R et al. (2014) Proton‐associated sucrose transport of mammalian solute carrier family 45: an analysis in Saccharomyces cerevisiae. Biochem. J. 464: 193‐201 [PMID:23506898]Vitavska O et al. (2013) The SLC45 gene family of putative sugar transporters. Mol. Aspects Med. 34: 655‐60 folic acid transporter [434], with lower affinity for heme. Folic acid accumulation is independent of Na+ or K+ ion concentrations, but driven by extracellular protons with an as yet undefined stoichiometry.Based on the proptypical member of this family, PCFT, this family includes proton‐driven transporters with 11 TM segments. SLC46A1 has been described to act as an intestinal proton‐coupled high‐affinity [PMID:24745983]Hou Z et al. (2014) Biology of the major facilitative folate transporters SLC19A1 and SLC46A1. Curr Top Membr 73: 175‐204 [PMID:24396145]Matherly LH et al. (2014) The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer. Drug Metab. Dispos. 42: 632‐49 [PMID:25877470]Wilson MR et al. (2015) Structural determinants of human proton‐coupled folate transporter oligomerization: role of GXXXG motifs and identification of oligomeric interfaces at transmembrane domains 3 and 6. Biochem. J. [PMID:21568705]Zhao R et al. (2011) Mechanisms of membrane transport of folates into cells and across epithelia. Annu. Rev. Nutr. 31: 177‐201 [PMID:23506878]Zhao R et al. (2013) Folate and thiamine transporters mediated by facilitative carriers (SLC19A1‐3 and SLC46A1) and folate receptors. Mol. Aspects Med. 34: 373‐85 603] and are suggested to be responsible for excretion of many drugs in the liver and kidneys.These proton:organic cation exchangers are predicted to have 13 TM segments [587]. MATE2 and MATE2‐B are inactive splice variants of MATE2‐K [370].DAPI has been used to allow quantification of MATE1 and MATE2‐mediated transport activity [[PMID:21923552]Damme K et al. (2011) Mammalian MATE (SLC47A) transport proteins: impact on efflux of endogenous substrates and xenobiotics. Drug Metab. Rev. 43: 499‐523 [PMID:23506899]Motohashi H et al. (2013) Multidrug and toxin extrusion family SLC47: physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2‐K. Mol. Aspects Med. 34: 661‐8 [PMID:27165417]Nies AT et al. (2016) Structure and function of multidrug and toxin extrusion proteins (MATEs) and their relevance to drug therapy and personalized medicine. Arch Toxicol 90: 1555‐84 [PMID:27317943]Wagner DJ et al. (2016) Polyspecific organic cation transporters and their impact on drug intracellular levels and pharmacodynamics. Pharmacol Res 111: 237‐46 [PMID:21457222]Yonezawa A et al. (2011) Importance of the multidrug and toxin extrusion MATE/SLC47A family to pharmacokinetics, pharmacodynamics/toxicodynamics and pharmacogenomics. Br. J. Pharmacol. 164: 1817‐25 439]. In addition, evidence suggests this 4TM‐containing protein associates with the V‐ATPase in lysosomes [407]. Recent studies confirm its lysosomal location and demonstrate that it has an important physiological function in macrophages ingesting senescent red blood cells (erythrophagocytosis), recycling heme (released from the red cell hemoglobin) from the phagolysosome into the cytosol, where the heme is subsequently catabolized to recycle the iron [565].HRG1 has been identified as a cell surface and lysosomal heme transporter [[PMID:23506900]Khan AA et al. (2013) Heme and FLVCR‐related transporter families SLC48 and SLC49. Mol. Aspects Med. 34: 669‐82 509], and later identified as a cell surface accumulation which exports heme from the cytosol [436]. A recent study indicates that an isoform of FLVCR1 is located in the mitochondria, the site of the final steps of heme synthesis, and appears to transport heme into the cytosol [96]. FLVCR‐mediated heme transport is essential for erythropoiesis. Flvcr1 gene mutations have been identified as the cause of PCARP (posterior column ataxia with retinitis pigmentosa (PCARP) [438].There are three paralogs of FLVCR1 in the human genome.FLVCR1 was initially identified as a cell‐surface attachment site for feline leukemia virus subgroup C [351], has been reported to function as a heme importer [141]. In addition, a congenital syndrome of proliferative vasculopathy and hydranencephaly, also known as Fowler's syndrome, is associated with a loss‐of‐function mutation in FLVCR2 [377].FLVCR2, most similar to FLVCR1 [52].The functions of the other two members of the SLC49 family, MFSD7 and DIRC2, are unknown, although DIRC2 has been implicated in hereditary renal carcinomas [Diamond Blackfan anemia[461].Non‐functional splice alternatives of FLVCR1 have been implicated as a cause of a congenital red cell aplasia, [PMID:23506900]Khan AA et al. (2013) Heme and FLVCR‐related transporter families SLC48 and SLC49. Mol. Aspects Med. 34: 669‐82 [PMID:21238504]Khan AA et al. (2011) Control of intracellular heme levels: heme transporters and heme oxygenases. Biochim. Biophys. Acta 1813: 668‐82 507], later termed Rag1‐activating protein 1, with a sequence homology predictive of a 4TM topology. The plant orthologues, termed SWEETs, appear to be 7 TM proteins, with extracellular N‐termini, and the capacity for bidirectional flux of D‐glucose[88]. Expression of mouse SWEET in the mammary gland was suggestive of a role in Golgi lactose synthesis [88].A mouse stromal cell cDNA library was used to clone C2.3 [[PMID:23506865]Wright EM. (2013) Glucose transport families SLC5 and SLC50. Mol. Aspects Med. 34: 183‐96 [PMID:21527736]Wright EM et al. (2011) Biology of human sodium glucose transporters. Physiol. Rev. 91: 733‐94 34, 118]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to steroid movement [168]. Bile acid transport is suggested to be facilitative and independent of sodium, potassium, chloride ions or protons . OSTα/OSTβ heterodimers have been shown to transport 3H]taurocholic aciddehydroepiandrosterone sulphateestrone‐3‐sulphatepregnenolone sulphate[ and 3H]dehydroepiandrosterone sulphate. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM 'ancillary' protein, both of which are thought to have intracellular C‐termini [347]. Bimolecular fluorescence complementation studies suggest the possibility of OSTα homo‐oligomers, as well as OSTα/OSTβ hetero‐oligomers .The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [α‐Ostβ. Dig Dis 29: 13‐7 [PMID:21691099]Ballatori N. (2011) Pleiotropic functions of the organic solute transporter Ostα‐OSTβ/SLC51: a transporter for steroid‐derived molecules. Mol. Aspects Med. 34: 683‐92 [PMID:23506901]Ballatori N et al. (2013) The heteromeric organic solute transporter, OST[PMID:21103970]Dawson PA. (2011) Role of the intestinal bile acid transporters in bile acid and drug disposition. Handb Exp Pharmacol 169‐203 riboflavin, also known as vitamin B2, is a precursor of the enzyme cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Riboflavin transporters are predicted to possess 10 or 11 TM segments.Although expressed elsewhere, RFVT3 is found on the luminal surface of intestinal epithelium and is thought to mediate uptake of dietary riboflavin, while RFVT1 and RFVT2 are thought to allow movement from the epithelium into the blood.[PMID:23506902]Yonezawa A et al. (2013) Novel riboflavin transporter family RFVT/SLC52: identification, nomenclature, functional characterization and genetic diseases of RFVT/SLC52. Mol. Aspects Med. 34: 693‐701 The SLCO superfamily is comprised of the organic anion transporting polypeptides (OATPs). The 11 human OATPs are divided into 6 families and ten subfamilies based on amino acid identity. These proteins are located on the plasma membrane of cells throughout the body. They have 12 TM domains and intracellular termini, with multiple putative glycosylation sites. OATPs mediate the sodium‐independent uptake of a wide range of amphiphilic substrates, including many drugs and toxins. Due to the multispecificity of these proteins, this guide lists classes of substrates and inhibitors for each family member. More comprehensive lists of substrates, inhibitors, and their relative affinities may be found in the review articles listed below.[PMID:23506880]Hagenbuch B et al. (2013) The SLCO (former SLC21) superfamily of transporters. Mol. Aspects Med. 34: 396‐412 [PMID:27936281]Lee HH et al. (2017) Interindividual and interethnic variability in drug disposition: polymorphisms in organic anion transporting polypeptide 1B1 . Br J Clin Pharmacol 83: 1176‐1184 [PMID:28299773]Murray M et al. (2017) Trafficking and other regulatory mechanisms for organic anion transporting polypeptides and organic anion transporters that modulate cellular drug and xenobiotic influx and that are dysregulated in disease. Br J Pharmacol 174 1908‐1924 [PMID:21854228]Obaidat A et al. (2012) The expression and function of organic anion transporting polypeptides in normal tissues and in cancer. Annu. Rev. Pharmacol. Toxicol. 52: 135‐51 [PMID:22013971]Roth M et al. (2012) OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br. J. Pharmacol. 165: 1260‐87 [PMID:28249706]Shitara Y et al. (2017) Preincubation‐dependent and long‐lasting inhibition of organic anion transporting polypeptide (OATP) and its impact on drug‐drug interactions. Pharmacol Ther Ezetimibe is used to reduce cholesterol absorption through inhibition of NPC1L1.NPC1L1 acts in the gut epithelium to allow the accumulation of dietary cholesterol through a clathrin‐dependent mechanism. [PMID:20809793]Jia L et al. (2011) Niemann‐pick C1‐like 1 (NPC1L1) protein in intestinal and hepatic cholesterol transport. Annu Rev Physiol 73: 239‐59 [PMID:26923679]Pirillo A et al. (2016) Niemann‐Pick C1‐Like 1 (NPC1L1) Inhibition and Cardiovascular Diseases. Curr Med Chem 23: 983‐99 [PMID:22480541]Wang LJ et al. (2012) Niemann‐Pick C1‐Like 1 and cholesterol uptake. Biochim Biophys Acta 1821: 964‐72