ANXA1 is a calcium-dependent phospholipid-binding protein that functions primarily as a ligand for formyl peptide receptors (FPR1/FPR2), activating downstream signaling cascades 12. It promotes chemotaxis of immune cells, actin cytoskeleton rearrangement, cell migration, and critically, resolution of inflammation and wound healing 34. ANXA1 exerts anti-inflammatory effects via multiple mechanisms: in endothelial cells and VSMCs, it prevents senescence and phenotype switching through FPR2-dependent pathways 56; in kidneys, intracellular ANXA1 inhibits NF-κB activation to resolve diabetic nephropathy 7; in microglia, Ac2-26 (ANXA1 mimetic) activates FPR2/ALX to enhance AMPK and inhibit mTOR, protecting against cerebral ischemia-reperfusion injury 2. Conversely, loss of ANXA1 has paradoxical tumor-suppressive effects: in esophageal and pancreatic cancers, ANXA1 loss prevents fibroblast and macrophage-mediated immunosuppression, enhancing antitumor immunity 18; in glioblastoma, ANXA1-FPR1 signaling between astrocytes and tumor cells drives immune evasion 9. ANXA1 is dysregulated in multiple cancer types and age-related cardiovascular diseases, making it a potential therapeutic target for both inflammatory diseases and selective cancers.