RAR-related orphan receptor C (RORC) is a key regulator of cellular differentiation, immunity, peripheral circadian rhythm as well as lipid, steroid, xenobiotics and glucose metabolism. RORC has intrinsic transcriptional activity and binds natural ligands like oxysterols that act as agonists (25-hydroxycholesterol) or inverse agonists (7-oxygenated sterols), enhancing or repressing transcriptional activity, respectively. RORC controls adipogenesis as well as adipocyte size and it modulates insulin sensitivity in obesity. In the liver, it has specific and redundant functions with RORA as a positive or negative modulator of the expression of genes involved in the metabolism of lipids, steroids and xenobiotics, such as SULT1E1. It also plays also a role in the regulation of hepatocyte glucose metabolism through the regulation of G6PC and PCK1. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804