Fibrinogen-like protein 2 (FGL2)

Fibrinogen-like protein 2 (FGL2) is a 439-amino acid member of the fibrinogen-related protein family, encoded by the FGL2 gene. FGL2 exists in two major forms: membrane-bound (mFGL2), a type II transmembrane protein primarily found on macrophages, endothelial cells, and T cells, and soluble (sFGL2), secreted primarily by T lymphocytes. The membrane-bound form functions as a prothrombinase enzyme, capable of directly converting prothrombin to thrombin without the classical clotting cascade, resulting in tissue fibrin deposition and vascular thrombosis, especially during viral infection or inflammation. The soluble form acts as a potent immunosuppressor, dampening T cell and dendritic cell responses, and promoting immune tolerance, notably through interactions with the inhibitory FcγRIIB receptor. FGL2 plays key roles in immune modulation, tissue inflammation, apoptosis, angiogenesis, and is implicated in the progression of multiple diseases—including cancer, viral hepatitis, organ transplantation outcomes, and some autoimmune and cardiovascular conditions. Human FGL2 is under investigation as both a biomarker for disease monitoring and a therapeutic target, with particular interest in immunomodulation, cancer therapy, and treatment of inflammatory and infectious diseases.

Other names

Fibrinogen-like protein 2FGL2FibroleukinFGL2 prothrombinase

Drugs targeting FGL2 generally seek to block its immunosuppressive (sFGL2) or procoagulant/prothrombinase (mFGL2) activities. Inhibitors can prevent immune escape in tumors by reducing FGL2-driven Treg and macrophage activity. Reducing FGL2 activity can prevent fibrin deposition and tissue inflammation in viral hepatitis.