More sophisticated genetic approaches using transgenic mice have helped to address the selective functional roles of different LTCCs.19, 22, 23 Constitutive deletion of Cacna1c was shown to result in embryonic lethality28 and conditional inactivation of Cav1.2 in forebrain structures was repeatedly associated with impairments in cognitive function.29, 30, 31, 32 More recently, haploinsufficiency and forebrain-specific deletion of Cacna1c were also associated with anxiety-like behavior33, 34 and sleep disturbances,35 two core endophenotypes of MDD and BPD. The gene discussed is CACNA1C; the disease is major depressive disorder.