[12] The first three-human isoforms of RORα were initially cloned and characterized as nuclear receptors in 1994 by Giguère and colleagues, when their structure and function were first studied.

[13] In the early 2000s, various studies demonstrated that RORα displays rhythmic patterns of expression in a circadian cycle in the liver, kidney, retina, and lung.

[16] In humans, 4 isoforms of RORα have been identified, which are generated via alternative splicing and promoter usage, and exhibit differential tissue-specific expression.

[17] This feedback loop regulating the expression of Bmal1 is thought to stabilize the core clock mechanism, helping to buffer it against changes in the environment.

[5] In contrast to RORα, RORβ is expressed in Central Nervous System (CNS) tissues involved in processing sensory information and in generating circadian rhythms while RORγ is critical in lymph node organogenesis and thymopoeisis.

T0901317 and SR1001, two synthetic ligands, have been found to be RORα and RORγ inverse agonists that suppress reporter activity and have been shown to delay onset and clinical severity of multiple sclerosis and other Th17 cell-mediated autoimmune diseases.

SR1078 has been discovered as a RORα and RORγ agonist that increases the expression of G6PC and FGF21, yielding the therapeutic potential to treat obesity and diabetes as well as cancer of the breast, ovaries, and prostate.