Zika virus (ZIKV) is a flavivirus transmitted by mosquitoes and sex. Outbreaks are linked to congenital neurodevelopmental defects, including microcephaly. Recent studies have revealed that ZIKV can infect neural stem cells and inhibit neurogenesis in mice and humans. However, the cellular mechanisms by which ZIKV disrupts brain development remain largely mysterious. We have found that ZIKV disrupts centrosome organization, a phenotype associated with inherited forms of microcephaly (MCPH). ZIKV infection induces supernumerary Centrin foci that accumulate the MCPH- associated protein CEP63, a critical regulator of centriole duplication. The nonstructural protease/helicase produced by ZIKV called NS3, localizes to the centrosome and binds to CEP63 and its interacting protein, CCDC14. Like ZIKV infection, expression of NS3 alone induces supernumerary Centrin foci that accumulate CEP63, suggesting that ZIKV NS3 interacts with and alters the function of the MCPH-associated protein CEP63 to disrupt centrosome organization in neural precursor cells. As centrosome defects cause human microcephaly, we propose that ZIKV-produced NS3 causes microcephaly by interacting with and abrogating the centrosomal function of the microcephaly protein CEP63. To understand how NS3 disrupts centrosome organization and how centrosome disorganization contributes to the development of microcephaly, we will investigate how NS3 localizes to the centrosome, how it acts at the centrosome to change its architecture, how altered centrosomal architecture changes the identity of human neural precursor cells, and how ZIKV-associated changes in centrosomes disrupt the innate immune response. Together, these studies will provide insights into the parallels between ZIKV-associated microcephaly and inherited forms of microcephaly, shedding light on the fundamental mechanisms by which centrosomes function during neurogenesis and providing candidate targets for inhibiting the deleterious effects of ZIKV on cortical development.