Higher L1 copy numbers have been observed in the human brain compared to other organs. Studies of animal models and human cell lines have shown that L1s become active in neural progenitor cells (NPCs), and that experimental deregulation of or overexpression of L1 increases somatic mosaicism. This phenomenon is negatively regulated by Sox2, which is downregulated in NPCs, and by MeCP2 and methylation of the L1 5' UTR. Human cell lines modeling the neurological disorder Rett syndrome, which carry MeCP2 mutations, exhibit increased L1 transposition, suggesting a link between L1 activity and neurological disorders. Current studies are aimed at investigating the potential roles of L1 activity in various neuropsychiatric disorders including schizophrenia, autism spectrum disorders, epilepsy, bipolar disorder, Tourette syndrome, and drug addiction. L1s are also highly expressed in octopus brain, suggesting a convergent mechanism in complex cognition.