Mutations occur during cell division in all somatic lineages due to the unavoidable DNA replication errors. Because neural stem cells continue to undergo cell division throughout human life, somatic mutations in human brain can arise during development and accumulate with the aging process. Although somatic diversity is an evident feature of the brain, the extent of somatic mutations affecting the neuronal structure and function and their contribution to neurological disorders remain largely unexplored. Recently, we and other groups have provided the molecular genetic evidence that brain somatic mutations indeed lead to the structural and functional abnormalities of the brain observed in several neurodevelopmental disorders. In this symposium, I will present our recent findings regarding brain somatic mutations as potential molecular lesions underlying various human brain disorders.