SNX15 is a sorting nexin family protein that regulates intracellular protein trafficking through endosomal compartments. As a phox homology (PX) domain-containing protein, SNX15 localizes to both membrane and cytosolic compartments 1 and associates with clathrin-coated pits and early endosomes 2. Its MIT domain exhibits calcium-dependent phosphoinositide-binding activity, enabling membrane association 3. Mechanistically, SNX15 links clathrin-mediated endocytosis to early endosome maturation independently of the APPL1 pathway, facilitating EGF receptor trafficking and degradative sorting 2. Overexpression of SNX15 disrupts endosomal morphology and impairs transferrin endocytosis and recycling 4, while altering the trafficking of insulin and hepatocyte growth factor receptors 1. Clinically, SNX15 has emerged as a therapeutic target in Alzheimer's disease: AAV-mediated SNX15 expression in transgenic AD mice reduces amyloid-β pathology and improves working memory by enhancing APP recycling to the cell surface, thereby decreasing amyloid-β generation 5. SNX15 also shows relevance to chr11 Chagas cardiomyopathy susceptibility through genetic association studies 6. Additionally, SNX15 was identified as a hub gene in cholangiocarcinoma with implications for cancer progression and immune suppression 7, and a novel RARA-SNX15 fusion has been reported in acute promyelocytic leukemia 8.