ANXA3 (annexin A3) is a 36-33 kDa calcium-dependent phospholipid-binding protein that functions as a phospholipase A2 inhibitor and anti-coagulant 1. Beyond these canonical roles, ANXA3 stabilizes the actin cytoskeleton to maintain endothelial barrier integrity during sepsis by preserving junction proteins zonula occludens-1, VE-cadherin, and claudin-5 2. In cancer, ANXA3 promotes tumor progression through multiple pathways: it reprograms tumor-associated macrophages toward an immunosuppressive M2 phenotype via AKT-GSK3β-β-catenin signaling, and ANXA3-rich exosomes inhibit ferroptosis in laryngeal cancer cells through ATF2-CHAC1 axis modulation, facilitating lymphatic metastasis 3. ANXA3 is overexpressed in colorectal cancer and correlates with tumor stem cell markers (CD133) and hypoxia signaling (HIF-1α), associating with larger tumors and advanced clinical stage 4. During hepatitis C infection, ANXA3 localizes to lipid droplets as an essential host factor for viral morphogenesis 5. Genome-wide association studies identify ANXA3 as a risk locus for IgA nephropathy, a progressive kidney disease, suggesting involvement in inflammatory pathways 6. ANXA3 elevation also correlates with obesity in Prader-Willi syndrome patients 7. These diverse functions position ANXA3 as a pleiotropic regulator of inflammation, cytoskeletal dynamics, and disease progression across multiple pathologies.