The retinoid X receptor (RXR)[1] is an important family of transcription factors that can combine with various nuclear receptors to form a protein dimer, which is often needed for those receptors to perform their functions. It is also a nuclear receptor which is activated by 9-cis retinoic acid, but whether its role as a direct endogenous receptor is important biologically is controversial.[2][3] It can also bind to 9-cis-13,14-dihydroretinoic acid, which may be an endogenous mammalian RXR-selective agonist.[4]Bexarotene is the only FDA-approved medication that selectively activates the RXRs while exhibiting negligible activity toward the retinoic acid receptors.[5]
RXR heterodimerizes with multiple nuclear receptors including CAR, FXR, LXR, PPAR,[6]PXR, RAR, TR, ER and VDR. RXRs are permissive co-receptors as only one of six alleles is needed for normal development and health.[7] Given this, it is difficult to extrapolate whether the RXR pathway has its own endogenous activity driven by 9-cis retinoic acid species or whether it merely participates in other pathways, predominantly the retinoic nuclear receptor pathway. Genomic knockout of the RXRs results in obesity resistance[8] while bexarotene treatment causes severe hypothyroidism,[9] suggesting that the RXR pathway functions at least to regulate the thyroid hormone receptor pathway.
