The voltage-gated Cav1.2 calcium channels respond to membrane depolarization by increasing the membrane permeability to Ca(2+), a major signal for cardiac muscle contraction, regulation of vascular tone and CREB-dependent transcriptional activation. CACNB2 is one of the four homologous genes coding for the auxiliary Cavβ subunits, which are important modulators of the Ca(2+) channel activity. Five serious mental disorders - autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia, - and three major cardiovascular diseases - hypertension, heart failure and sudden cardiac death, - have recently been linked to the CACNB2 gene coding for the Cavβ2 subunits. Here I will focus on the Cavβ2-specific molecular determinant β2-CED as an emerging pharmacological target.