ANXA3 (annexin A3) is a 36–33 kDa calcium-dependent phospholipid-binding protein that functions as an inhibitor of phospholipase A2 and possesses anti-coagulant properties. The protein also cleaves cyclic inositol phosphates and regulates actin cytoskeleton dynamics. In normal physiology, ANXA3 stabilizes the endothelial cytoskeleton and maintains vascular integrity; ANXA3 knockout mice showed exacerbated sepsis outcomes with increased lung injury and vascular permeability 1. ANXA3 is dysregulated across multiple malignancies. Elevated ANXA3 expression associates with breast cancer progression, particularly in triple-negative tumors, correlating with increased cell proliferation and lymph node metastasis 2. In laryngeal squamous cell carcinoma, ANXA3-rich exosomes from tumor-associated macrophages inhibit ferroptosis via an ATF2-CHAC1 axis, promoting lymphatic metastasis 3. Similarly, elevated ANXA3 expression in colon carcinoma correlates with tumor size, lymphatic metastasis, and clinical stage 4. In glioblastoma, ANXA3 overexpression associates with intrinsic temozolomide resistance 5. Beyond cancer, ANXA3 is a genome-wide associated locus for IgA nephropathy 6 and is upregulated in obese Prader-Willi syndrome patients 7. Recent evidence suggests ANXA3 serves as a sphingolipid metabolism-related biomarker for acute myocardial infarction diagnosis 8. ANXA3 regulates tumor progression through multiple pathways including PI3K/Akt, NF-κB, and HIF-1 signaling 9.