rxr

Retinoid X receptors (RXRs) are a subfamily of nuclear receptors that regulate gene transcription in response to retinoids and other signals. In mammals, three RXR genes encode RXR-α (RXRA), RXR-β (RXRB), and RXR-γ (RXRG), with widespread expression in liver, adipose tissue, brain, and immune cells. The receptors have the classic nuclear receptor structure: an N-terminal activation function domain, a central DNA-binding domain with two zinc fingers, and a C-terminal ligand-binding domain that mediates dimerization and transcriptional activation.

RXRs function as transcription factors that primarily act as dimerization partners. They can form homodimers or heterodimers with other nuclear receptors such as RARs, PPARs, LXRs, FXRs, and VDRs, enabling regulation of diverse gene networks. The DNA elements they recognize are RXR response elements (RXREs), often direct repeats separated by one or two nucleotides (DR1, DR2). The activity of RXR-containing dimers can depend on the ligand status of the partner receptor.

Natural ligands include retinoic acids, notably 9-cis-retinoic acid, though physiologic relevance varies by context. Synthetic compounds that selectively activate RXRs, called rexinoids (for example bexarotene), are used experimentally and clinically.

Roles for RXRs span development, metabolism, adipogenesis, lipid and glucose homeostasis, and immune function; they contribute to neural and retinal biology and may influence circadian regulation. Clinically, rexinoids such as bexarotene are approved for certain skin lymphomas, while RXR agonists are investigated for metabolic and neurodegenerative diseases; their use can produce adverse effects such as hyperlipidemia and hypothyroidism.