Kv7.2 R325G mutant subunits, when incorporated in heteromeric channels with Kv7.2 and Kv7.3 subunits at a ratio reproducing the genetic balance of epilepsy-affected patients, exerted dominant-negative effects, enhanced current suppression by PIP2 depletion with VSP, and slowed current recovery kinetics after VSP turnoff; all these results, beside confirming the molecular mechanism of the primary dysfunction, also provide strong support for a significant role of the decreased PIP2 sensitivity in severe epilepsy pathogenesis in patients carrying the R325G variant. This evidence concerns the gene KCNQ2 and epilepsy.