In the present study we investigated whether the CASK/P2X3 complex was altered and functionally linked to sensitization of P2X3 receptors in transgenic knock-in (KI) mice exhibiting a gain-of-function phenotype of voltage-gated CaV2.1 (P/Q-type) calcium channels, due to a R192Q missense mutation in the channel α1 subunit that causes familial hemiplegic migraine type 1 (FHM-1)[7,8]. Here, CASK is linked to familial or sporadic hemiplegic migraine.