AbstractKv2.1 voltage‐gated potassium channels consist of two types of α‐subunits: (a) electrically‐active Kcnb1 α‐subunits and (b) silent or modulatory α‐subunits plus β‐subunits that, similar to silent α‐subunits, also regulate electrically‐active subunits. Voltage‐gated potassium channels were traditionally viewed, mainly by electrophysiologists, as regulators of the electrical activity of the plasma membrane in excitable cells, a role that is performed by transmembrane protein domains of α‐subunits that form the electric pore. Genetic studies revealed a role for this region of α‐subunits of voltage‐gated potassium channels in human neurodevelopmental disorders, such as epileptic encephalopathy. The N‐ and C‐terminal domains of α‐subunits interact to form the cytoplasmic subunit of heterotetrameric potassium channels that regulate electric pores. Subsequent animal studies revealed the developmental functions of Kcnb1‐containing voltage‐gated potassium channels and illustrated their role during brain development and reproduction. These functions of potassium channels are discussed in this review in the context of regulatory interactions between electrically‐active and regulatory subunits.