SNX17 is a critical endosomal adaptor protein that regulates surface protein recycling by recognizing NPxY motifs in cargo cytoplasmic tails 1 and binding phosphatidylinositol 3-phosphate on endosomal membranes 2. SNX17 adopts an autoinhibited conformation where its C-terminal tail is sequestered; cargo binding displaces this tail, enabling association with the Retriever complex subunits VPS35L and VPS26C 34. This SNX17-Retriever-CCC-WASH axis prevents lysosomal degradation and promotes recycling of over 120 surface proteins including integrins, receptors, and transporters 5. SNX17 maintains normal cell surface levels of APP and LRP1 26, and critically regulates LDLR recycling—PCSK9 blocks SNX17-mediated LDLR salvage, driving receptor degradation 7. SNX17 dysregulation drives disease pathogenesis. In hepatocellular carcinoma, SNX17 overexpression promotes proliferation and metastasis via retromer-dependent STAT3 activation and c-Myc upregulation 8. In immunotherapy, elevated SNX17 confers anti-PD-1 resistance by stabilizing RUNX2, increasing uridine degradation in the tumor microenvironment and suppressing CD8+ T cell function 9. SNX17-dependent endocytic cargo in neurons includes neurodegenerative disease risk factors 10. These findings establish SNX17 as both a central recycling hub and therapeutic target across multiple pathologies.