Fibrinogen-like protein 1 (FGL1)

Fibrinogen-like protein 1 (FGL1) is a secreted glycoprotein highly expressed in hepatocytes and regulated by inflammatory stimuli like IL-6. It mediates hepatocyte proliferation, controls systemic inflammation, and is upregulated in response to tissue injury and regeneration. Structurally, FGL1 contains a fibrinogen-related domain but lacks the classical clotting functions of other family members. Most notably, it is a major ligand for lymphocyte-activation gene 3 (LAG-3) on T cells, acting as an immune checkpoint to suppress T-cell activity and promote tumor immune escape. Cancer patients with high plasma FGL1 often show resistance to anti-PD-1/PD-L1 therapies. Emerging strategies for cancer immunotherapy target the FGL1-LAG-3 axis to restore anti-tumor immunity. It is also implicated as an anti-inflammatory agent in preclinical models of autoimmune disease, including rheumatoid arthritis. FGL1 expression may serve as a predictive biomarker for immunotherapy response and, due to its metabolic functions, is linked to obesity and liver disease. Safety data in animals suggest low toxicity with short-term therapeutic usage, but manipulation could disturb immune homeostasis, necessitating further evaluation.

Other names

HepassocinHFREP1Hepatocyte-derived fibrinogen-like protein-1

Immune checkpoint modulation: Blockade of FGL1-LAG-3 interaction enhances T cell activity and anti-tumor immunity. EGFR/ERK pathway activation: Restores hepatocyte proliferation and liver repair. Regulation through post-translational modification (e.g., acetylation impacts protein stability).