VPS33B belongs to the STXBP/unc-18/SEC1 family. It may play a role in vesicle-mediated protein trafficking to lysosomal compartments and in membrane docking/fusion reactions of late endosomes/lysosomes. VPS33B is ubiquitous; highly expressed in testis and low expression in the lung. Defects in VPS33B are the cause of arthrogryposis-renal dysfunction-cholestasis syndrome (ARC) [MIM:208085]. ARC is an autosomal recessive multisystem disorder, characterized by neurogenic arthrogryposis multiplex congenita, renal tubular dysfunction and neonatal cholestasis with bile duct hypoplasia and low gamma glutamyl transpeptidase activity. Platelet dysfunction is common.
Late endosome membrane; Peripheral membrane protein; Cytoplasmic side. Lysosome membrane; Peripheral membrane protein; Cytoplasmic side. Note: Cytoplasmic, peripheral membrane protein associated with late endosomes/lysosomes. Colocalizes with M.tuberculosis PtpA in the cytosol of tuberculosis-infected macrophages and associates with phagosomes. Colocalizes in clusters with VIPAS39 at cytoplasmic organelles.