KCNT2 encodes a sodium-activated and chloride-activated potassium channel that produces rapidly activating outward rectifier K+ currents 1. The channel contributes to regulating neuronal excitability 2 through its activity at the plasma membrane. Functionally, KCNT2 localizes to intracellular compartments where it mediates potassium ion transport and chloride-activated potassium channel activity. Pathogenic KCNT2 variants cause developmental and epileptic encephalopathy 57 (DEE57), characterized by intellectual disability (ranging from mild to severe/profound), early-onset seizures, altered muscle tone, and dysmorphic features 3. Variants exhibit either gain-of-function (GoF) or loss-of-function (LoF) mechanisms, each with distinct pharmacological profiles: quinidine and fluoxetine block GoF variants, while loxapine and riluzole selectively activate or block LoF variants 3. Recent genome-wide association studies identified KCNT2 as genetically associated with neuropathic pain intensity in diabetic polyneuropathy 4. Furthermore, KCNT2 knockout mice demonstrate increased neuronal excitability and enhanced seizure susceptibility, suggesting the channel provides neuroprotection 5. The discovery of variant-specific functional properties underscores the clinical importance of in vitro functional assessment to enable targeted, mechanism-based therapeutic approaches for KCNT2-related disorders.