The overarching goal of the Isom and Jiang laboratories is to understand the molecular basis of genetic epilepsy. Our objective here is to combine the expertise of our two research groups to discover novel epilepsy mutations in potassium channel genes and to understand their contributions to neuronal hyperexcitability in order to provide useful platforms for future drug discovery. Potassium channels, encoded by more than 90 genes, are the largest ion channel family. Potassium channel proteins are critical to the establishment and maintenance of neuronal excitability in brain, and thus it is not surprising that mutations in potassium channel genes are important factors in epileptogenesis in human patients, especially in pediatrics. Clinical studies have identified 17 potassium channel gene mutations linked to epilepsy, including pediatric epileptic encephalopathy. Studies of cellular and animal models predict that additional potassium channel genes will be implicated in human epilepsy. Understanding the effects of these mutations on channel function and on brain network excitability is critical to the successful development of novel therapeutics in the future.