Rev-Erb beta (Rev-Erbβ), also known as nuclear receptor subfamily 1 group D member 2 (NR1D2), is a member of the Rev-Erb protein family. Rev-Erbβ, like Rev-Erbα, belongs to the nuclear receptor superfamily of transcription factors and can modulate gene expression through binding to gene promoters. Together with Rev-Erbα, Rev-Erbβ functions as a major regulator of the circadian clock. These two proteins are partially redundant. Current research suggests that Rev-Erbβ is less important in maintaining the circadian clock than Rev-Erbα; knock-out studies of Rev-Erbα result in significant circadian disruption but the same has not been found with Rev-Erbβ. Rev-Erbβ compensation for Rev-Erbα varies across tissues, and further research is needed to elucidate the separate role of Rev-Erbβ. This gene is expressed in the central and peripheral nervous system, spleen, mandibular maxillary processes, and blood islands. Rev-Erbβ plays a major role in the conduction of inductive signals to aid in controlling differentiating neurons. Discovery Rev-Erbβ was discovered in 1994, when B. Dumas et al. isolated its cDNA, naming the new receptor BD73. The name Rev-Erbβ was coined a few months later in a paper by Eva Enmark, Tommi Kainu, Markku Tapio Pelto-Huikko, and Jan Ǻke Gustafsson where they isolated Rev-Erb alpha cDNA in a rat brain. A new isoform of Rev-Erbβ, named Rev-Erbβ 2, was discovered using rat cDNA a few months later in 1995 by N. Giambiagi and colleagues. They found it to be identical to Rev-Erbβ 1, except that the Rev-Erbβ 1 protein is 195 amino acids longer than Rev-Erbβ 2. However, further research has indicated that the discovered Rev-Erbβ 2 cDNA was likely a splice variant of the Nr1d2 gene that arose through alternative splicing and the use of a different polyadenylation site. Genetics and Evolution In mammals, the NR1D2 (nuclear receptor subfamily 1 group D member 2) gene encodes the protein Rev-Erbβ. Unlike NR1D1, the strand opposite NR1D2 does not have any significant reading frames, and the gene is located on the forward strand of chromosome 3. Despite their different locations, the NR1D1 and NR1D2 genes are highly homologous and are paralogs within the genome. In humans, the NR1D2 gene itself contains 10 exons which form 5 splice variants (NR1D2-201 - NR1D2-205), ranging from 5231 base pairs (NR1D2-201) to 600 base pairs (NR1D2-204). However, only NR1D2-201 produces a functional protein. In mammals, NR1D2 (Rev-Erbβ) is expressed throughout the body and with high expression in several tissues, including the