FGL-2

Fibrinogen-like protein 2 (FGL-2) is a transmembrane serine prothrombinase and secreted immunomodulator of the fibrinogen-related protein family, produced by regulatory T cells, macrophages, endothelial cells and dendritic cells. In its membrane-bound form, FGL2 directly cleaves prothrombin to thrombin independent of the classic coagulation cascade, driving fibrin deposition in microvasculature-a mechanism central to the pathogenesis of xenograft rejection, viral hepatitis (murine hepatitis virus-induced fulminant hepatitis) and glomerulonephritis. As a secreted homodimer binding FcγRII (CD32) on antigen-presenting cells, FGL2 inhibits dendritic cell maturation, antigen presentation and T-cell proliferation, suppressing Th1 responses and experimental autoimmune encephalomyelitis, while promoting maternal-fetal tolerance and corneal allograft survival. In cancer, FGL2 is a key effector of Treg-mediated immunosuppression in hepatocellular carcinoma and gliomas, associated with exhausted CD8+ T-cell phenotypes and poor survival, making FGL2 blockade an emerging immunotherapy concept alongside its anticoagulation-independent roles.