KCNQ5 encodes a voltage-gated potassium channel subunit broadly expressed in brain and involved in regulating neuronal excitability. It forms heteromeric channels with KCNQ3 to generate M-type currents, slowly activating potassium conductances that control subthreshold electrical excitability of neurons 12. KCNQ5 also associates with KCNQ1 in vascular smooth muscle, contributing to vasoconstriction. Channel activation requires both membrane depolarization and the signaling lipid phosphatidylinositol 4,5-bisphosphate (PIP2) 3. Recent evidence reveals KCNQ5 controls perivascular adipose tissue-mediated vasodilation through oxylipid signaling 4. Clinically, KCNQ5 variants cause neurodevelopmental disorders with contrasting mechanisms. De novo missense variants produce gain-of-function effects causing developmental and epileptic encephalopathy or intellectual disability, with severity correlating to the magnitude of voltage-dependence shifts 5. Conversely, loss-of-function variants—including nonsense mutations, truncations, and some missense changes—underlie genetic generalized epilepsies with absence seizures 6. KCNQ5 loss-of-function mouse models exhibit seizures and abnormal cortical activity, confirming pathogenicity 5. Channel activators including retigabine and ezogabine represent therapeutic targets for these epilepsy syndromes 2.