SNX5 (sorting nexin 5) is a BAR and PX domain-containing retromer component that mediates multiple intracellular trafficking pathways. Structurally, SNX5 interacts with phosphatidylinositol-enriched endosomal membranes and functions as part of the SNX-BAR retromer subcomplex, which deforms membranes into tubular carriers for retrograde transport from endosomes to the trans-Golgi network 1. Beyond canonical retromer functions, SNX5 has acquired specialized tissue-specific roles: in endothelial cells, nuclear estrogen receptor-α upregulates SNX5 expression, promoting insulin transcytosis to skeletal muscle and glucose tolerance 2; in muscle, SNX5 stabilizes PKA regulatory subunit RI-α on early endosomes, controlling myogenic differentiation through ordered PKA signaling 3. SNX5 coordinates glucose transporter GLUT4 trafficking via interaction with CHC22 clathrin and ERGIC tether p115, establishing a Golgi-bypass route essential for glucose metabolism 4. During viral infection, SNX5 specifically activates endosomal PI3KC3-C1 to generate phosphatidylinositol-3-phosphate, initiating virus-induced autophagy independently of basal pathways 5. In gastric cancer, SNX5 overexpression promotes malignancy by preventing LRP5 degradation, sustaining Wnt/β-catenin signaling 6. SNX5 participates in autophagosomal component recycling via the recycler complex 7. These context-dependent functions establish SNX5 as a critical integrator of endosomal transport, immune responses, metabolic regulation, and disease progression.