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The interplay between retinoic acid receptor-related orphan receptors and human diseases

The retinoic acid receptor-related orphan receptors (RORs) are an important subfamily of transcriptional regulators of the nuclear receptors superfamily. Their discovery over a decade ago by gene cloning strategy have revealed three major isoforms of these orphan receptors in animals. Generation and analyses of isoform-specific ROR null mice have provided revealed-vital roles for the RORs in animals. The RORs undoubtedly participate in a host of biological functions such a metabolism, immunity, development and differentiation, angiogenesis, circadian clock, xenobiotic/drug metabolism and other tissue physiologies for optimal animal survival. Moreover, intense work in the last one decade also revealed a host of human diseases being modulated by the RORs. A number of diseases, such as cancer, autoimmune diseases, inflammation, osteoporosis, metabolic syndrome etc., strongly support the involvement of RORs in their onset and progression. By involving in such diseases, the RORs are indeed a critical factor for optimal cell function and are being intensely investigated as novel targets for drug interventions in the treatment of various diseases. This review focuses on the current knowledge and status about RORs in a number of human disease conditions.