Hepassocin, also known as hepatocyte-derived fibrinogen-related protein 1 (HFREP-1) and Fibrinogen-Like Protein 1 (FGL1) (1), is a liver-specific secreted protein belonging to the fibrinogen superfamily, whose members share a fibrinogen domain at their C-termini (2). Human Hepassocin/FGL1 is a secreted homodimer consisting of 312 amino acids (aa) with a 22 aa signal sequence and a 290 aa mature protein (3). Mouse and rat Hepassocin/FGL1 share approximately 84% and 83% amino acid identity with human Hepassocin/FGL1, respectively. Human Hepassocin/FGL1 binds LAG-3 through its fibrinogen-like domain independently of MHC class II (4). Hepassocin/FGL1 inhibits antigen-specific T cell activation, with its elevated presence in plasma of cancer patients indicating poor prognoses (4). Other than this role in cancer progression, Hepassocin/FGL1 also has restorative function for liver cells, as it is upregulated during liver regeneration following partial hepatectomy (5), and stimulates proliferation of hepatocytes in vivo and improves prognoses with fulminant hepatic failure in rats (6). Its expression is regulated in Hep G2 cells by interleukin-6 (IL-6) and is found in the serum in both bound and unbound states as an acute phase reactant (7).
