ANXA1 is a calcium-dependent phospholipid-binding protein that primarily functions through activation of formyl peptide receptors (FPR1/FPR2) to regulate immune and metabolic homeostasis. It promotes chemotaxis of granulocytes and monocytes, actin cytoskeleton rearrangement, and cell migration, while also promoting resolution of inflammation and wound healing. In cerebral ischemia-reperfusion injury, an ANXA1-derived peptide (Ac2-26) shifts microglia/macrophage polarization toward anti-inflammatory phenotypes via FPR2/ALX-dependent AMPK-mTOR signaling, improving outcomes in acute ischemic stroke patients 1. ANXA1 shows context-dependent roles in cancer: loss of ANXA1 in epithelial cells during esophageal cancer progression allows fibroblast transformation into cancer-associated fibroblasts through reduced FPR2 signaling 2, while high ANXA1 expression in pancreatic cancer-associated macrophages suppresses antitumor immunity by promoting efferocytosis and inhibiting cGAS-STING pathway activation 3. In intrahepatic cholangiocarcinoma, ANXA1 stabilizes the glutamine metabolism enzyme GOT1, promoting tumor growth 4. Outside oncology, Ac2-26 supplementation inhibits obesity-related adipogenesis through PDLIM7-mediated SMAD4 degradation 5 and mitigates atrial fibrillation susceptibility in obese mice via AMPK-dependent metabolic stress relief 6. Recent evidence also suggests ANXA1 upregulation of UCP1 alleviates diabetic nephropathy through improved mitochondrial homeostasis 7. These findings position ANXA1 signaling as a therapeutic target in metabolic disease, stroke, and select cancer contexts.