FGL2 (fibrinogen-like 2) is a fibrinogen superfamily member with dual functional forms: membrane-associated FGL2 (mFGL2) exhibits prothrombinase activity and is expressed by inflammatory macrophages, dendritic cells, and T cells 1, while soluble FGL2 (sFGL2) is primarily produced by regulatory T cells 1. Primary function involves immune regulation and coagulation. Mechanistically, FGL2 interacts with TLR4 to activate NF-κB, p38-MAPK, and NLRP3 inflammasome signaling in macrophages 2, and directly binds mucolipin 3 to regulate calcium influx and autophagy, promoting neutrophil extracellular trap formation 3. sFGL2 suppresses immune activation through FcγRIIB and FcγRIII receptors, downregulating CD86 on antigen-presenting cells and limiting T cell activation 4. Disease relevance spans multiple pathologies: FGL2 aggravates nonalcoholic steatohepatitis progression 2, exacerbates liver injury in fulminant viral hepatitis 3, and promotes tumor growth by attenuating immune infiltration in melanoma and ovarian cancer 4. In non-small cell lung adenocarcinoma and gliomas, high FGL2 expression predicts worse prognosis 56, while in gastric cancer, FGL2 is part of immunosuppressive M2 macrophage signatures associated with poor survival 7. Conversely, FGL2 secretion by bone marrow CD7+ monocytes promotes beige fat thermogenesis via PKA signaling, protecting against weight regain 8. Clinically, FGL2 emerges as a prognostic biomarker and therapeutic target across inflammatory and neoplastic diseases.