Retinoic acid receptor-related orphan receptor alpha (RORα)

Retinoic acid receptor-related orphan receptor alpha (RORα) is a member of the nuclear receptor superfamily functioning as a ligand-activated transcription factor[3][6][8]. RORα binds as a monomer to specific DNA sequences, modulating gene expression involved in circadian rhythm, immune responses, metabolism (including lipid and glucose homeostasis), cellular differentiation, and development (notably neural and immune cell development)[3][5][8]. Natural ligands include oxysterols and cholesterol, which can act as agonists or inverse agonists to modulate its transcriptional activity[4][8]. RORα is implicated in diverse diseases related to its regulatory roles in metabolism, immunity, inflammation, and the nervous system; thus, it is an emerging therapeutic target for conditions such as autoimmune diseases, metabolic syndrome, neurodevelopmental disorders, and cancer[3][5][7][9]. Various synthetic ligands are under investigation, acting as agonists or inverse agonists to modulate RORα function in these disease settings[3].

Other names

RORαRAR-related orphan receptor alphaNR1F1 (nuclear receptor subfamily 1, group F, member 1)RORA gene productNuclear receptor ROR-alphaRetinoic acid receptor-related orphan receptor alpha

Agonists: activate transcription of target genes by stabilizing the active conformation of the ligand-binding domain. Inverse agonists or antagonists: repress transcriptional activity, often by disrupting co-activator binding or recruiting co-repressors. Modulation of gene expression involved in immune cell differentiation (especially Th17 cells) and metabolic pathways.