SCN3A encodes Nav1.3, the pore-forming α subunit of a voltage-gated sodium channel that mediates action potential depolarization in excitable tissues 1. Nav1.3 selectively conducts Na+ ions across the plasma membrane in response to voltage changes, enabling electrical signal propagation in neurons and regulating cell excitability and secretory responses 2. SCN3A is transiently expressed during early fetal cortical development, particularly in neural progenitor cells and migrating neurons 3. Pathogenic SCN3A variants cause SCN3A-related neurodevelopmental disorder, characterized by treatment-resistant early-onset epilepsy (typically within the first year of life) and severe developmental delay 4. Notably, malformations of cortical development, including polymicrogyria, occur in >75% of affected individuals 4, suggesting a critical role in prenatal cortical folding and neuronal migration 3. Most pathogenic missense variants (91%) exhibit gain-of-function effects, with increased persistent current and altered voltage-dependent activation 4. Disease-associated variants cluster in transmembrane segments 4-6 of channel domains II-IV 4. Gain-of-function SCN3A variants produce aberrant neuronal firing patterns including paroxysmal bursting and action potential failures 5. Nav1.3-selective blockers normalize these abnormal firing patterns, offering potential therapeutic approaches for SCN3A-related encephalopathy 5. SCN3A variants are among the most frequently identified genetic causes in polymicrogyria cohorts 6.