PROJECT SUMMARY/ABSTRACT Neuropsychiatric disorders represent a leading cause of disability, affecting nearly 19% of the US population. Only 9% of neuropsychiatric drugs entering clinical trials reach the market, which is one of the lowest success rates across all therapeutic areas. Fundamental differences between the neurobiology of rodents and humans have been proposed to account for translational failures in development of effective therapeutic strategies to mitigate neurological or neurodegenerative diseases or disorders. Rodent behavioral assays are also variably effective in predicting clinically effective neuropsychiatric drugs. Nonhuman primates (NHPs) are recognized as a valuable, clinically relevant alternative to span the gap between rodents and humans in the development of therapies designed to advance brain health. Among NHPs, the common marmoset or Callithrix jacchus (cj) affords a highly tractable option because of its small size, short lifespan, production of multiple offspring/year and accurate recapitulation of human neuroanatomy. However, the ultimate utility of the marmoset model remains in its infancy due to the paucity of efficient tools to facilitate studies requiring genetic modification, especially those needed to recapitulate complex aspects of brain health. To address this urgent need, we will combine close proximity to one of two NIH-designated Marmoset Breeding Colonies (U24 MH123422, funded under RFA-MH-20-145) maintained at the Southwest National Primate Research Center and leading expertise in brain health and disease in general and the neurogenetics of epilepsy in particular. In this diversity supplement, we will perform the experiments outlined in Aim 3 of the parent U01 application, which is to assess the impact of ARX mutations on marmoset cortical neuron development and migration. This aim is designed to advance the utility of the marmoset model for brain research based on the development of PSC-derived brain organoids and specific knowledge of the neurological impact of ARX mutations.