Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport across cell membranes, playing an important role in hepatic fatty acid uptake (  , ). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates, which prevents fatty acid efflux from cells and might drive more fatty acid uptake (  , ). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation or triglyceride synthesis . Can also activate branched-chain fatty acids such as phytanic acid and pristanic acid . May contribute to the synthesis of sphingosine-1-phosphate . Does not activate C24 bile acids, cholate and chenodeoxycholate . In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol . However, it is not critical for THCA activation and bile synthesis in vivo .
Exhibits both long-chain fatty acids (LCFA) transport activity and acyl CoA synthetase towards very long-chain fatty acids (, ). Shows a preference for generating CoA derivatives of n-3 fatty acids, which are preferentially trafficked into phosphatidylinositol .
Exhibits long-chain fatty acids (LCFA) transport activity but lacks acyl CoA synthetase towards very long-chain fatty acids.
Subcellular locations: Endoplasmic reticulum membrane, Peroxisome membrane, Cell membrane, Microsome
Expressed in liver, kidney, placenta, intestine, brain, heart, and colon ( ). Predominantly expressed in liver .
Expressed in liver, placenta, and intestine, but much lower relative to isoform 1.