HNF4 is a member of the nuclear hormone receptor family of transcription factors. It binds DNA as a homodimer and, although initially believed to be an orphan receptor, its activity may be modulated by the binding of fatty acyl-CoA thioesters. The existence of a ligand for HNF4 has been somewhat controversial, but linoleic acid (LA) has been identified as the endogenous ligand of native HNF4 expressed in mouse liver. In addition, HNF4 is acetylated, phosphorylated, and can bind SMADS 3 and 4, suggesting that its activity may be controlled by multiple pathways. HNF4 generally acts as a positive transcriptional regulator of many hepatocyte genes and can rescue the expression of liver genes in dedifferentiated hepatoma cell lines[1].