NR2E1 is an orphan nuclear receptor that functions primarily as a transcriptional regulator in the central nervous system and retina. As a sequence-specific DNA-binding protein, NR2E1 binds to extended core motif half-sites (5'-AAGGTCA-3') and regulates target genes essential for neural development 1. NR2E1 controls neural stem cell self-renewal and maintains stemness in the brain and visual system 2. In retinal development, NR2E1 regulates PTEN-Cyclin D expression by recruiting the histone demethylase LSD1 to suppress PTEN at its promoter, promoting retinal progenitor proliferation 3. NR2E1 acts primarily as a transcriptional repressor through interactions with co-repressors including atrophin-1, LSD1, and HDAC, though co-activator interactions with p300 have also been identified 4. NR2E1 restrains cellular senescence by regulating the polycomb protein CBX7 and suppressing senescence markers p16 and p21 5. Functionally, NR2E1-null mice exhibit cortical hypoplasia and retinal dystrophy, while human mutations in regulatory regions are associated with cortical malformations and microcephaly 6. Genetic variants in NR2E1 are implicated in schizophrenia susceptibility 7. Additionally, NR2E1 is involved in brain tumor biology, promoting self-renewal of brain tumor-initiating cells 3.