Estrogen-related receptor alpha (ERRalpha/NR3B1) is an orphan nuclear receptor that controls transcription of genes involved in fatty acid oxidation, glucose metabolism, and mitochondrial biogenesis. The receptor protein contains a non-conserved amino terminal domain (NTD), a central zinc finger DNA binding domain, and a ligand-binding domain. The carboxy-terminal AF2 helix motif of ERRalpha contains binding sites for nuclear receptor coactivators PGC-1alpha and PGC-1beta. Research studies demonstrate that ERRalpha transcriptional activity is regulated through phosphorylation and sumoylation within the NTD.