Background：Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system(UPS), autophagy and the endoplasmic reticulum-associated protein degradation(ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding(via UBA domain) to their polyubiquitin chains and by interacting(via ubiquitin-like domain) with the subunits of the proteasome(PubMed:10983987). Plays a role in the ERAD pathway via its interaction with ER-localized proteins FAF2/UBXD8 and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome(PubMed:24215460, PubMed:18307982). Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy-related protein LC3 from the cytosolic form LC3-I to the membrane-bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome-lysosome fusion(PubMed:19148225, PubMed:20529957). Negatively regulates the endocytosis of GPCR receptors: AVPR2 and ADRB2, by specifically reducing the rate at which receptor-arrestin complexes concentrate in clathrin-coated pits(CCPs)(PubMed:18199683).
