KCNQ5 encodes a voltage-gated potassium channel subunit broadly expressed in the brain that regulates neuronal excitability 1234. The protein forms functional channels with KCNQ3 to generate M-type currents, a slowly activating potassium conductance critical for controlling subthreshold neuronal excitability 23. KCNQ5 also forms channels with KCNQ1 that may contribute to vasoconstriction 5, and recent evidence demonstrates its central role in perivascular adipose tissue-mediated vasodilation through oxylipin-dependent activation of smooth muscle KV7.5 channels 6. Channel gating requires phosphatidylinositol 4,5-bisphosphate (PIP2) binding at two distinct sites between voltage-sensing and pore domains 78. De novo KCNQ5 variants cause developmental and epileptic encephalopathy through both gain-of-function (hyperpolarized activation, slowed deactivation) and loss-of-function mechanisms 9. Loss-of-function variants are also implicated in genetic generalized epilepsies with absence seizures, functioning through decreased current density and dominant-negative effects 10. KCNQ5 is widely distributed in temporal neocortex and hippocampus 11, making it a therapeutic target for anticonvulsants and potentially other neurological disorders.