Recent studies from our group and a team of collaborators have used cryo-EM to demonstrate the surprising gating role of the Kv3.1 cytoplasmic T1 domain, the structural basis of a developmental epileptic encephalopathy caused by the Kv3.2-C125Y variant and the mechanism of action of positive allosteric modulators involving unexpected interactions and conformational changes in Kv3.1 and Kv3.2. The gene discussed is KCNC2; the disease is developmental and epileptic encephalopathy.