This review focuses on the vascular dysfunction in prediabetes and MetS and summarizes the most recent knowledge regarding alterations in the expression or activity of the proteins that form the functional unit (CaV1.2, SERCA pump, RyRs, and BKCa channels) that participates in regulating the vascular tone, in experimental models with characteristics of prediabetes and MetS. The gene discussed is CACNA1C; the disease is prediabetes syndrome.