SCN1A and epilepsy: In 1 study, mutant KCNT1 homomers revealed a more marked gain of function than mutant WT heteromers.13 A significant remaining question is how KCNT1 gain-of-function variants with predicted effects on neuronal hyperpolarization result in epilepsy.28 Altered voltage sensitivity may result in KCNT1 channels opening at more depolarized potentials, allowing a persistent hyperpolarizing current, with resultant interneuronal disinhibition as reported in SCN1A-related epilepsy.39 Conversely, increased repolarization permitting more frequent and rapid action potentials may also play a role.27,34