KCNQ2 encodes the pore-forming subunit of voltage-gated potassium M-channels, which assemble with KCNQ3 as heterotetramers to generate the M-current 123. This slowly activating potassium conductance critically regulates neuronal excitability by controlling resting membrane potential, shaping action potentials, and impeding repetitive firing 42. The channel exhibits selective cation permeability (K⁺ > Rb⁺ > Cs⁺ > Na⁺) and is suppressed by muscarinic acetylcholine receptor activation 25. KCNQ2 dysfunction causes diverse neurodevelopmental disorders ranging from benign familial neonatal seizures to severe epileptic encephalopathy and autism spectrum disorders 67. Pathogenic variants reduce M-current conductance, producing hyperexcitable neuronal networks with increased burst duration and synaptic connectivity 7. However, emerging evidence suggests KCNQ2 loss-of-function also impairs early neuronal maturation by causing depolarized resting potentials and reduced action potential generation 8. Beyond seizure disorders, KCNQ2 dysfunction contributes to motor neuron hyperexcitability in ALS/FTD through TDP-43-dependent mis-splicing 9. KCNQ2 activators including retigabine, cannabidiol, and investigational compounds show therapeutic potential by restoring channel function and rescuing hyperexcitable phenotypes 10117.