Epsin-1

Epsin-1 (EPN1) is an endocytic adapter protein that binds phosphatidylinositol 4,5-bisphosphate-enriched membranes to facilitate clathrin-coated pit formation and receptor-mediated endocytosis (UniProt: Q9Y6I3). The protein modifies membrane curvature and plays a central role in the internalization of cell-surface receptors.

In Alzheimer's Disease, Epsin-1 shows ambiguous regulation across subcellular fractions. Quantitative proteomics analysis of post-mortem AD brain tissue compared to age-matched controls revealed a mean log₂FC of 0.0092 across two fractions, indicating minimal and inconsistent change (Chaparral AD proteomics). This modest variation across subcellular compartments—particularly P2, P3, S2, and S3 fractions in TMT-labeled DDA proteomics—suggests Epsin-1 levels are largely preserved in AD, though compartment-specific alterations cannot be ruled out.

Given Epsin-1's role in endocytic trafficking and its relative stability in AD pathology, changes in its subcellular localization or activity state may be more relevant than protein abundance shifts in disease pathogenesis.