TR4 is a NR2 Hepatocyte NF4-Like nuclear hormone receptor and transcription factor related to the orphan receptors TR2, COUP-TFI, and ARP-1. TR4 has been shown to affect the proliferation and maturation of brain structures, neurogenesis, the regulation of myeloid progenitor cell proliferation and development, and retinoid-mediated signaling pathways. TR4 binds to target DNA as a homodimer or a monomer, and has been shown to affect transcription of ciliary neurotrophic factor receptor (CNTFR alpha), luteinizing hormone receptor, and human steroid 21-hydroxylase genes. During development, the expression of TR4 in human and rat brain correlates with the progression of neuronal maturation. TR4 becomes progressively restricted to the hypothalamus and cerebellum in older embryos and adults. Recently, it has been shown that TR4 can suppress estrogen receptor function via direct protein-protein interaction. Three rat and two human TR4 mRNA splice variants have been documented.