Estrogen-related receptor (ERR) (ERR)

The Estrogen-related receptors (ERRs) are a subfamily of orphan nuclear receptors, including ERRα, ERRβ, and ERRγ, that function as constitutive transcription factors. Despite their structural similarity to the classical estrogen receptors (ERα and ERβ), ERRs do not bind natural estrogens and instead regulate gene expression by binding to estrogen-related response elements (ERREs) [3, 6]. They play a central role in energy homeostasis by controlling mitochondrial biogenesis, oxidative phosphorylation, and fatty acid oxidation, often in coordination with the PGC-1 family of coactivators [3, 18]. In disease, ERRα is frequently overexpressed in various cancers, such as breast and prostate cancer, where it promotes metabolic reprogramming and is associated with poor clinical outcomes [11, 17]. Conversely, ERRγ is vital for maintaining high-energy demand tissues like the heart and skeletal muscle [3, 6]. Therapeutic strategies targeting ERRs include the use of inverse agonists to inhibit ERRα in cancer and agonists to enhance metabolic function in conditions like obesity and heart failure [9, 15]. While several synthetic ligands have been developed for research, ERRs remain a significant area of drug discovery for metabolic and oncological indications [15, 18].

Other names

ERRsNR3BEstrogen-related receptor alphaEstrogen-related receptor betaEstrogen-related receptor gammaESRRAESRRBESRRGNR3B1NR3B2NR3B3

Modulation of transcriptional activity through agonism, antagonism, or inverse agonism of the nuclear receptor to regulate metabolic and proliferative gene networks.