Hepatocyte nuclear factor 4alpha (HNF4alpha) is a transcription factor that belongs to the steroid hormone receptor superfamily and is enriched in liver. HNF4alpha, in association with PGC-1alpha, activates gluconeogenic genes such as phosphoenolpyruvate carboxykinase and glucose-6-phosphatase genes in fasted livers. Conditional knockout of the HNF4alpha gene in the mouse liver destroys lipid homeostasis and leads to lipid accumulation in the liver and a reduction of serum cholesterol and triglyceride levels. Mutations in HNF4alpha have been linked to maturity-onset diabetes of the young (MODY).