2000). Besides, the A454T mutation (placed in the intracellular loop connecting domains I and II (LI‐II) of the CaV2.1 α1A channel subunit, and associated to both early‐onset progressive ataxia (Cricchi et al. 2007) and the relief of migraine aura symptoms (Serra et al. 2010)) prevents the negative modulation of CaV2.1 channels by SNARE proteins and decreases channel coupling to exocytosis, thus revealing the importance of LI‐II structural integrity in the CaV2.1‐SNAREs functional interaction (Serra et al. 2010). The gene discussed is CACNA1A; the disease is migraine disorder.