CHD8 is an ATP-dependent chr14-remodeling factor that regulates transcription through nucleosome repositioning and chr14 structure modification 1. It functions as a transcription repressor by recruiting histone H1 to target genes and suppresses p53-mediated apoptosis, while also negatively regulating Wnt signaling through beta-catenin regulation. CHD8 modulates alternative splicing in genes involved in neuronal differentiation, cell cycle, and DNA repair, and enables H3K36me3-coupled transcription elongation. CHD8 mutations are strongly associated with autism spectrum disorder (ASD), ranking among the most highly penetrant ASD risk genes 23. Loss-of-function variants in CHD8 cause severe cognitive impairment in autistic individuals (88% with cognitive impairment), with CHD8 showing male-biased de novo enrichment 32. Animal models reveal that CHD8 haploinsufficiency disrupts cortical neuronal development, particularly affecting GABAergic and deep-layer excitatory neurons asynchronously 4. Conversely, CHD8 duplication causes behavioral hyperactivity, microcephaly, and impaired neuronal differentiation through aberrant enhancer binding 5. CHD8 mutations are implicated in intellectual developmental disorder with autism and macrocephaly, making it a critical regulator of normal neurodevelopment.