NR1F1; Retinoid related orphan receptor alpha (ROR alpha) is a NR1 Thyroid Hormone Like Receptor. ROR alpha has been shown to affect the development of the central nervous system. Deletion of ROR alpha in mice causes severe impairment in the differentiation of cerebellar Purkinje neurons and results in the "staggerer" phenotype. ROR alpha has been suggested as a potential target in the treatment of chronic inflammatory diseases, including atherosclerosis and rheumatoid arthritis. Within the ROR alpha group there are ROR alpha 1, 2, 3, and 4. These isotypes have been shown to differ in only their amino terminus, and their spatiotemporal expression appears to be under isoform specific regulation. ROR alpha isoforms have the same DNA binding domain but display different DNA binding specificities. ROR alpha 1 binds to and constitutively activates transcription from a large subset of ROR elements, while ROR alpha 2 recognizes ROR elements with strict specificity and displays weaker transcriptional activity. The structure of the ligand binding domain (LBD) of ROR alpha and a potential natural ligand have been elucidated. ROR alpha expression has been documented in human adipose, brain, breast, heart, liver, lung, muscle, ovary, PBLs, prostate, small intestine, spleen and testis. Research has shown that these proteins are key factors in the regulation of many physiological processes such as cell growth and differentiation. ROR alpha is also critical for proper cerebellar development, modulation of gene expression in response to hypoxic stress, and migratory capacities of cancer cells.