KCNMA1 encodes the pore-forming α subunit of the large conductance calcium and voltage-activated potassium (BK) channel 1. This channel mediates potassium export in response to both membrane depolarization and increased cytosolic calcium levels, playing critical roles in regulating neuronal excitability and muscle contractility 1. BK channels are widely distributed across tissues with highest expression in brain and muscle 1. KCNMA1 mutations cause a spectrum of neurological channelopathies collectively termed "KCNMA1-linked channelopathy" 1. These mutations can produce both gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity 1. Primary clinical manifestations include seizures, movement disorders, developmental delay, and intellectual disability 1. Notably, paroxysmal nonkinesigenic dyskinesia (PNKD3) predominantly segregates with GOF variants, while neurodevelopmental abnormalities and additional movement disorders are more common with LOF variants 2. Recent evidence indicates that specific KCNMA1 variants, such as D434G and N999S encoding GOF channels, cause seizure and PNKD3 3. Beyond neurological disease, KCNMA1 mutations have been newly identified as a rare genetic cause of neonatal diabetes mellitus 4. The variant-defined functional classification of KCNMA1 mutations enables precision therapeutic approaches tailored to GOF versus LOF alterations 3.