Spermatogenesis-defective protein 39 homolog

VIPAS39 (spermatogenesis-defective protein 39 homolog) is a 493-amino-acid protein proposed to function in endosomal maturation and vesicular trafficking through association with VPS33B and the HOPS complex (UniProt: Q9H9C1). In epithelial cells, it participates in RAB11A-dependent recycling and apical-basolateral polarity maintenance; additional roles include lysosomal trafficking and potential regulation of E-cadherin expression.

VIPAS39 is involved in fundamental cellular trafficking pathways. Pathogenic variants cause arthrogryposis, renal dysfunction and cholestasis syndrome 2 (ARCS2; MIM 613404), a multisystem developmental disorder affecting joints, kidneys, and biliary function (UniProt: Q9H9C1).

VIPAS39 is down-regulated in Alzheimer's disease brain. Post-mortem AD brain tissue shows reduced VIPAS39 abundance compared to age-matched controls, with a mean log2 fold-change of −0.27 (Chaparral AD proteomics). This downregulation was detected across a single subcellular fraction in TMT-labeled, data-dependent acquisition proteomics. The functional consequence of VIPAS39 reduction in AD pathology remains unclear but may relate to impaired endosomal-lysosomal trafficking.