COUP transcription factors have been cloned in several species and identified as orphan members of the steroid/thyroid hormone receptor superfamily. COUP-TFI (also designated COUP or EAR-3) and ARP-1 (also designated COUP-TFII) exhibit highly regulated and overlapping expression in most tissues. COUP-TFs are highly expressed in the developing and central nervous system, suggesting that these factors may be important in neural development and differentiation. COUP-TFs can compete for binding to response elements which are common to other members of this family, including RAR, RXR, PPAR, HNF-4, VDR and TR. They have been shown to act as negative regulators as well as initiators of transcription.