Vacuolar protein sorting-associated protein 37A

VPS37A (vacuolar protein sorting-associated protein 37A) is a 397-amino-acid component of the ESCRT-I complex, a machinery essential for vesicular trafficking and the sorting of ubiquitinated cargo into multivesicular bodies (UniProt: Q8NEZ2). The protein functions in endocytic regulation and may participate in cell growth and differentiation processes.

VPS37A is primarily implicated in spastic paraplegia 53 (SPG53), a neurodegenerative disorder characterized by progressive lower-limb weakness and spasticity, occasionally accompanied by cognitive decline and additional neurological complications (UniProt: Q8NEZ2). The gene's role in intracellular trafficking and neuronal integrity reflects its relevance to neurodegenerative disease.

In Alzheimer's disease, VPS37A is significantly downregulated in post-mortem brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.17 across subcellular fractions in TMT-labeled proteomics analysis. This reduction may reflect disrupted vesicular trafficking and ESCRT-mediated cargo sorting in AD pathology, processes implicated in amyloid and tau clearance.