Sorting nexin-5

Sorting nexin-5 (SNX5) is a membrane-binding protein that mediates intracellular trafficking through interactions with phosphatidylinositol lipids. It functions as part of the retromer SNX-BAR subcomplex, which orchestrates retrograde transport from endosomes to the trans-Golgi network and endosome-to-plasma membrane recycling. SNX5 also participates in receptor trafficking, including EGFR and IGF2R sorting, and plays roles in macropinocytosis and E-cadherin regulation (UniProt: Q9Y5X3).

SNX5 localizes to multiple subcellular compartments involved in endosomal recycling and cargo degradation pathways. No inherited disease associations are documented in UniProt, though retromer dysfunction has broad implications for membrane protein homeostasis and lysosomal integrity.

SNX5 is upregulated in Alzheimer's disease post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.175 (Chaparral AD proteomics). This elevation was measured across subcellular fractions from human post-mortem brain using quantitative proteomics, suggesting a potential compensatory or pathological increase in endosomal trafficking capacity in AD neuropathology.