Vacuolar protein sorting-associated protein 16B (VPS16B) (VPS16B)

Vacuolar protein sorting-associated protein 16B (VPS16B), also known as VIPAR or SPE-39, is a critical regulator of intracellular vesicle trafficking and organelle biogenesis. It functions primarily by forming a stable complex with the Sec1/Munc18 (SM) protein VPS33B, which together facilitate the docking and fusion of vesicles with target membranes, such as late endosomes and lysosomes [2, 13]. In megakaryocytes, this complex is essential for the biogenesis of alpha-granules, which store proteins vital for blood clotting and wound healing [2, 5]. Mutations in the VIPAS39 gene, which encodes VPS16B, lead to Arthrogryposis, Renal dysfunction, and Cholestasis (ARC) syndrome type 2, a severe multisystem disorder characterized by the absence of platelet alpha-granules, liver disease, and renal defects [8, 14]. The protein also plays a significant role in maintaining apical-basolateral polarity in epithelial cells by regulating the trafficking of apical proteins [11, 12]. While there are currently no approved drugs targeting VPS16B, it is a significant focus of research for understanding inherited platelet disorders and developing potential gene therapies for ARC syndrome [7, 9].

Other names

VIPAS39VIPARSPE-39SPE39hSPE-39Spermatogenesis-defective protein 39 homologVPS33B-interacting protein, apical-basolateral polarity regulator

Forms a complex with VPS33B to facilitate SNARE-mediated vesicle fusion and protein sorting, specifically during the maturation of alpha-granules in megakaryocytes and the maintenance of apical-basolateral polarity in epithelial cells.