TBR1 (T-box brain transcription factor 1) is a critical transcriptional regulator that controls multiple aspects of cortical development and neuronal specification 1. The protein functions as a transcriptional repressor involved in neuronal migration, laminar and areal identity, and axonal projection formation during brain development 2. TBR1 regulates the expression of several autism spectrum disorder (ASD) candidate genes and shares regulatory targets with other ASD-associated transcriptional regulators, with binding sites particularly enriched near brain-expressed genes 3. Mechanistically, TBR1 disruption leads to altered cortical layer formation, reduced anterior commissure development, and changes in neuronal cell populations 4. Heterozygous loss-of-function and missense mutations in TBR1 are associated with neurodevelopmental disorders characterized by intellectual disability, autism spectrum traits, and structural brain malformations including frontal pachygyria and hippocampal dysplasia 52. Clinical studies indicate TBR1 mutations contribute to approximately 1% of sporadic ASDs and represent a significant cause of moderate to severe intellectual disability 61. The gene's critical role in cortical development makes it an important diagnostic target for neurodevelopmental conditions with cognitive impairment and autistic features.