Cytoplasmic adapter protein that plays a critical role in clathrin-mediated endocytosis which is important in processes such as internalization of cell receptors, synaptic transmission or removal of apoptotic cells. Recruits AP-2 and attaches clathrin triskelions to the cytoplasmic side of plasma membrane leading to clathrin-coated vesicles (CCVs) assembly ( ). Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature . In addition to binding to clathrin, mediates the endocytosis of small R-SNARES (Soluble NSF Attachment Protein REceptors) between plasma membranes and endosomes including VAMP2, VAMP3, VAMP4, VAMP7 or VAMP8 ( ). In turn, PICALM-dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors . Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP-CTF) (, ).
Subcellular locations: Cell membrane, Membrane, Clathrin-coated pit, Golgi apparatus, Cytoplasmic vesicle, Clathrin-coated vesicle, Nucleus
Colocalized with clathrin in the Golgi area . Interaction with PIMREG may target PICALM to the nucleus in some cells .
Expressed in all tissues examined.