SNX9 is a multifunctional membrane-binding scaffold protein that orchestrates endocytic trafficking and membrane remodeling through coordinated protein-protein and lipid interactions. Structurally, SNX9 contains BAR-PX domains that bind phosphatidylinositol lipids (particularly PI(4,5)P2) and an SH3 domain that recruits dynamin and N-WASP to endocytic sites 1. Mechanistically, SNX9 stimulates dynamin GTPase activity and oligomerization while activating Arp2/3 complex-mediated actin polymerization, enabling both clathrin-dependent and clathrin-independent endocytosis 2. Beyond classical endocytosis, SNX9 mediates mitochondrial-derived vesicle (MDV) biogenesis through post-translational modifications; β-hydroxybutyrylation of SNX9 enhances MDV formation and mitochondrial homeostasis 3, while SNX9-dependent MDVs selectively transport undamaged mitochondrial proteins to extracellular vesicles, preventing inflammatory DAMP release 4. SNX9 also regulates fumarate-induced mtDNA release and innate immune activation via MDV-dependent pathways 5. Clinically, SNX9 inhibition alleviates CD8 T cell exhaustion and enhances anti-tumor immunity 6, while SNX9-targeting improves wound healing in diabetic models by reducing MDV-induced oxidative stress 7. These findings establish SNX9 as a critical node linking metabolism, vesicular trafficking, immune function, and disease pathogenesis.