Sorting nexin-6

Summary

Sorting nexin-6 (SNX6) is a 406-amino acid protein involved in multiple stages of intracellular trafficking (UniProt: Q9UNH7). It functions as a component of the retromer membrane-deforming SNX-BAR subcomplex, which mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network and is involved in endosome-to-plasma membrane recycling. SNX6 additionally regulates BACE1 retrograde transport, E-cadherin sorting and degradation, and EGFR degradation.

SNX6 localizes to membrane compartments enriched in phosphatidylinositol lipids and participates in vesicle remodeling and dynactin-mediated cargo transport. The protein's roles in lysosomal sorting and endosomal trafficking position it within broader cellular quality control and protein recycling pathways (UniProt: Q9UNH7).

In Alzheimer's disease, SNX6 is down-regulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.56 (Chaparral AD proteomics). This reduction was observed in a single fraction from a TMT-labeled quantitative proteomics experiment examining four subcellular fractions. The decreased expression may reflect altered endosomal-lysosomal trafficking dynamics in AD pathology.