Voltage-gated Ca²⁺ (Ca_V) channels are ubiquitously expressed and function as Ca²⁺ conducting pores in the plasma membrane¹. Based on their electrophysiological and pharmacological properties, Ca²⁺ channels have traditionally been classified into L, T, N, P, Q, and R types². L-type Ca²⁺ channels are heteromultimers composed of four independently encoded proteins, the pore-forming α1 subunit, which triggers Ca²⁺ flow across the membrane, and the auxiliary subunits α2δ, γ, and β³. The Ca²⁺ channel α2δ subunit is a heavily glycosylated protein that is encoded by a single gene and post-translationally cleaved to yield α2 and δ subunits linked by a disulfide bond with a single transmembrane segment⁴.

The α2δ subunit regulates many functional aspects of Ca²⁺ channels, such as gating, regulating voltage dependent kinetics, and increasing functional channel density on the plasma membrane⁵. There are four proteins that comprise Ca_Vα2δ: Ca_Vα2δ1, Ca_Vα2δ2, Ca_Vα2δ3 and Ca_Vα2δ4⁶. Ca_Vα2δ4 participates in the regulation of membrane expression of Ca_V channels. It is predominantly expressed in certain types of endocrine cells. It is also detected in the erythroblasts in the fetal liver, in the cells of the zona reticularis of the adrenal gland and in the basophiles of the pituitary⁷. Defects in Ca_Vα2δ4 are the cause of retinal cone dystrophy 4 (RCD4). RCD4 is characterized by minimal symptoms except for slowly progressive reduction in visual acuity⁸.