Vacuolar protein sorting-associated protein 45

Vacuolar protein sorting-associated protein 45 (VPS45) is a 570-amino acid protein involved in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network (UniProt: Q9NRW7). The protein facilitates intracellular transport and sorting of proteins destined for various cellular compartments.

In non-neurological contexts, VPS45 mutations are associated with severe congenital neutropenia-5 (SCN5), an autosomal recessive immunodeficiency disorder characterized by neutropenia and impaired neutrophil function (UniProt: Q9NRW7). The protein's role in vesicular trafficking suggests broader relevance to cellular homeostasis across tissues.

VPS45 shows elevated expression in Alzheimer's Disease brain tissue compared to age-matched controls (Chaparral AD proteomics). Post-mortem analysis using TMT-labeled quantitative proteomics across four subcellular fractions (P2, P3, S2, S3) demonstrated upregulation with a mean log2 fold-change of 0.41. This increased abundance in AD brain may reflect compensatory trafficking responses or alterations in vesicular dynamics associated with neurodegeneration.