SCN8A encodes Nav1.6, a voltage-gated sodium channel alpha subunit primarily expressed in neuronal tissues that mediates sodium ion transport and action potential generation 1. The channel plays critical roles in axonal function, including localization to nodes of Ranvier and the axon initial segment, where it controls membrane depolarization during action potentials 1. SCN8A mutations cause a spectrum of neurodevelopmental and epilepsy disorders with clear genotype-phenotype correlations. Gain-of-function missense variants cause focal or multifocal seizures with early onset (median 4 months), ranging from benign familial infantile epilepsy with normal cognition to severe developmental and epileptic encephalopathy with profound intellectual disability and pharmacoresistance 2. Conversely, loss-of-function variants predominantly cause generalized epilepsy with absence seizures and later onset (median 42 months) 2. The severity of electrophysiological dysfunction correlates with clinical severity in gain-of-function cases 2. Patients with gain-of-function variants respond significantly better to sodium channel blockers than other antiepileptic drugs, supporting precision medicine approaches 32. Emerging therapeutic strategies include antisense oligonucleotides that reduce SCN8A mRNA abundance in mouse models of developmental and epileptic encephalopathy 4.