F13A1 encodes the A subunit of coagulation factor XIII (FXIII), a transglutaminase activated by thrombin and calcium that catalyzes gamma-glutamyl-epsilon-lysine cross-links between fibrin chains, mechanically stabilizing fibrin clots and protecting them from fibrinolysis 1. Beyond hemostasis, F13A1 cross-links alpha-2-plasmin inhibitor and fibronectin to fibrin, supporting wound healing and angiogenesis through VEGFR2 and integrin Ξ±VΞ²3 interactions 2. Recent studies reveal F13A1's immunomodulatory roles. F13A1-positive macrophages drive metabolic-associated steatohepatitis (MASH) progression via the PKM2/HIF1A pathway, with F13A1 directly interacting with pyruvate kinase M2 to promote pro-inflammatory phenotypes 3. In obesity, F13A1 expression increases in adipose tissue and associates with inflammatory pathways and tissue remodeling 4. F13A1+ macrophages are enriched in multiple primary lung cancers, exhibiting immunosuppressive characteristics that promote tumor growth 5. Clinically, severe F13A1 deficiency causes rare but severe hemorrhagic diathesis with delayed wound healing and recurrent pregnancy loss 1. The Val34Leu polymorphism associates with recurrent pregnancy loss, particularly in Asian populations 6. RUNX1 transcription factor regulates F13A1 expression in platelets and megakaryocytes; RUNX1 deficiency decreases F13A1 and impairs clot contraction 7.