CHD5 is an ATP-dependent chr1-remodeling factor that functions as a component of the NuRD complex, recognizing H3K27me3 and regulating gene transcription through histone binding. In the nervous system, CHD5 plays a critical role in neurogenesis by activating genes promoting neuronal differentiation while maintaining H3K27me3-mediated repression of non-neuronal lineage genes 1. CHD5 also regulates spermatogenesis through histone acetylation and histone-to-protamine replacement during chr1 condensation 2. Heterozygous CHD5 variants cause Parenti-Mignot neurodevelopmental syndrome, characterized by intellectual disability (64%), language deficits (81%), epilepsy (62%), behavioral disturbances (69%), and motor delay (56%) 3. The gene was identified as a high-confidence NDD-associated gene through large-scale genomic analysis 4. Additionally, CHD5 acts as a tumor suppressor frequently inactivated through 1p36 deletions and promoter methylation in neuroblastoma and multiple adult cancers including glioma, breast, colon, lung, and prostate cancers 5. CHD5 inhibits neuroblastoma metastasis partly through upregulation of the metastasis-suppressing gene PLCL1, with p53 pathway involvement 6. The CHD5 polymorphism rs9434741 represents a genetic risk factor for male infertility in non-obstructive azoospermia 7.