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 (PubMed:
10436022, PubMed:
16262731, PubMed:
27574975). Furthermore, regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature (PubMed:
25898166). 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 (PubMed:
22118466, PubMed:
21808019, PubMed:
23741335). In turn, PICALM- dependent SNARE endocytosis is required for the formation and maturation of autophagic precursors (PubMed:
25241929). Modulates thereby autophagy and the turnover of autophagy substrates such as MAPT/TAU or amyloid precursor protein cleaved C-terminal fragment (APP- CTF) (PubMed:
25241929, PubMed:
24067654).
