RORB (RAR-related orphan receptor B) is a transcription factor that plays critical roles in neuronal development, particularly in retinal cell differentiation and cortical patterning. The protein regulates gene expression through sequence-specific DNA binding and exhibits tissue-specific expression patterns, with high levels in specific neuronal populations 1. RORB functions as a key regulator of cortical development, particularly in prefrontal cortex patterning where it serves as a layer 4 marker and is involved in retinoic acid signaling pathways 2. The gene also plays important roles in pancreatic β-cell function, where RORB expression correlates positively with insulin secretion and negatively with HbA1c levels 3. Disease relevance is significant, as heterozygous RORB variants are associated with idiopathic generalized epilepsy, particularly absence seizures with intellectual disability 45. RORB+ neurons show selective vulnerability in Alzheimer's disease, with these cells being preferentially lost during disease progression and accumulating intracellular amyloid-β 6. The gene has also been implicated in bipolar disorder susceptibility, with genetic variants showing association with disease risk 7. Functionally, RORB variants demonstrate impaired protein function through shortened axonal morphology in experimental studies 4.