Although further research, including electrophysiological analysis, is required to confirm this hypothesis, interestingly, a gain-of-function CaV2.1 genetic variant in that precise S6 pore area (ΔF1502) associated to congenital ataxia and hemiplegic migraine, has been reported to improve voltage-dependent gating of CaV2.1 by strongly decreasing the voltage threshold for channel opening, fastening activation kinetics, and slowing down both the deactivation and the inactivation of the channel [13,20]. This evidence concerns the gene CACNA1A and familial or sporadic hemiplegic migraine.