VPS33B encodes a Sec1/Munc18 family protein that plays crucial roles in vesicle-mediated protein trafficking and membrane fusion at late endosomes and lysosomes 1. The protein forms a stable complex with VIPAR, distinct from the CORVET/HOPS complexes that contain the related VPS33A protein 2. VPS33B is required for proper trafficking of lysyl hydroxylase 3 (LH3), a collagen-modifying enzyme, through interactions with Rab11a and Rab25 proteins 3. Additionally, VPS33B is essential for platelet α-granule formation, as demonstrated by studies of arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome 4. Disease-causing mutations in VPS33B result in multiple clinical phenotypes including ARC syndrome, characterized by arthrogryposis, renal tubular dysfunction, and cholestasis 56, and autosomal recessive keratoderma-ichthyosis-deafness (ARKID) syndrome 3. Pathogenic variants impair protein interactions with Rab proteins and disrupt collagen modification processes, leading to defective epidermal barrier formation and abnormal platelet morphology. Recent reports suggest VPS33B variants may also affect von Willebrand factor levels, expanding the clinical spectrum 7.