Nuclear Receptor Subfamily 2 Group E Member 3 (NR2E3): Role in Retinal Development and Disease.

is a nuclear hormone receptor gene required for the correct development of the retinal rod photoreceptors. Expression of NR2E3 protein in rod cell precursors suppresses cone-specific gene expression and, in concert with other transcription factors including NRL, activates the expression of rod-specific genes. Pathogenic variants involving cause a spectrum of retinopathies, including enhanced S-cone syndrome, Goldmann-Favre syndrome, retinitis pigmentosa, and clumped pigmentary retinal degeneration, with limited evidence of genotype-phenotype correlations. A common feature of -related disease is an abnormally high number of cone photoreceptors that are sensitive to short wavelength light, the S-cones. This characteristic has been supported by mouse studies, which have also revealed that loss of function causes photoreceptors to develop as cells that are intermediate between rods and cones. While there is currently no available cure for -related retinopathies, there are a number of emerging therapeutic strategies under investigation, including the use of viral gene therapy and gene editing, that have shown promise for the future treatment of patients with variants and other inherited retinal diseases. This review provides a detailed overview of the current understanding of the role of in normal development and disease, and the associated clinical phenotypes, animal models, and therapeutic studies.