FGL1

FGL1, or fibrinogen-like protein 1, is a secreted glycoprotein encoded by the human FGL1 gene. It is a member of the fibrinogen-related protein family and contains a fibrinogen-like globular domain. A signal peptide directs its secretion by hepatocytes, making the liver a major source of circulating FGL1 under normal and stressed conditions.

Function and roles

FGL1 was initially described as a hepatocyte-derived factor with mitogenic activity that can promote hepatocyte proliferation and liver regeneration after injury. In addition to its hepatic effects, FGL1 is best known as a ligand for the immune receptor LAG-3 (lymphocyte activation gene-3). Interaction with LAG-3 on activated T cells inhibits T cell activation and proliferation, contributing to immune tolerance in physiological settings and facilitating immune evasion by some tumors. This LAG-3–FGL1 axis has drawn attention as an immune checkpoint pathway relevant to cancer immunotherapy.

Expression and regulation

FGL1 is predominantly expressed in the liver, with detectable levels in the bloodstream. Expression can be modulated by liver injury and inflammatory signals, and its circulating concentration tends to reflect hepatic secretory activity. Beyond the liver, FGL1 expression has been reported in other tissues under certain conditions, reflecting a broader but less well defined role.

Clinical and research context

Because FGL1 serves as a ligand for LAG-3, it is a focus of research on immune checkpoints and cancer therapy. Therapies aiming to disrupt the FGL1–LAG-3 interaction are being explored to enhance anti-tumor immunity, while the hepatic mitogenic properties of FGL1 continue to be investigated in liver regeneration and liver disease contexts.