K99 Admin Supplement Project Summary The idea that ion channels can disrupt cortex formation is a new area of study, particularly when exploring the mechanisms activated at a cellular level. Since dividing progenitor cells and newborn neurons in the developing cerebral cortex rely on ions for controlling cellular processes, I will test the new hypothesis that disrupted activity of specific ion fluxes is critical to cortex assembly. Proof of the existence of developmental channelopathies in the brain has remained elusive due to the heterogenous nature of cortical malformations and the fact that they are often are under extreme negative pressure evolutionarily. Given that I am describing and categorizing brain disorders that improve our understanding of disease mechanisms and the treatment of conditions related to malformation of cortical development (MCD), the significance of this work to human research will immediately improve health is immediate as the results generated by this genetic testing for diagnosed disorders. I will complete this research with a combination of both proven and innovative strategies, including: Aim 1) Completed (K99 Aim 1, year 1) Aim 2) Characterizing a novel mouse model for a developmental channelopathy; Aim 3) Development of a novel physiological assay in developing human cerebral organoids.