ERRγ: a Junior Orphan with a Senior Role in Metabolism

Estrogen-related receptor (ERR)gamma is an orphan nuclear hormone receptor that belongs to the ERR subfamily of transcription factors. No endogenous ligand has been identified to date. ERR gamma possesses ligand-independent transcriptional activity that is regulated by co-regulator interactions, and post-translational modifications (PTMs). Recent data from animal models have established ERR gamma as a crucial mediator of multiple endocrine and metabolic signals. ERR gamma plays important roles in pathological conditions such as insulin resistance, alcoholic liver injury, and cardiac hypertrophy, and controls energy metabolism in the heart, skeletal muscle, and pancreatic b cells. These findings corroborate the importance of ERR gamma in metabolic homeostasis, and suggest that ERR gamma is a good target for the treatment of metabolic diseases.