Voltage-dependent calcium channel subunit alpha-2/delta-1 is a protein that in humans is encoded by the CACNA2D1 gene.

The CACNA2D1 gene is located on chromosome 7q21.11–q22, spanning genomic coordinates approximately 81,946,444 to 82,443,956 on the reverse (minus) strand according to the GRCh38 genome build. This gene is part of a family that includes several transcript variants generated by alternative splicing, highlighting its considerable genetic complexity. The promoter region of CACNA2D1 is characterized by a GC-rich sequence and multiple binding sites for the Sp1 transcription factor, rather than a typical TATA box.

In mammals, alpha-2/delta proteins are classified into four subtypes, each encoded by a separate but closely related gene: CACNA2D1 (this gene), CACNA2D2, CACNA2D3, and CACNA2D4.

Alternate transcriptional splice variants of this gene have been observed, but have not been thoroughly characterized.

Voltage-dependent calcium channels are composed of a complex of four subunits—alpha-1 (ion conducting subunit), alpha-2/delta (this gene, auxiliary subunit), beta, and gamma—in a 1:1:1:1 stoichiometry.

CACNA2D1 is a gene that encodes the alpha-2/delta-1 subunit of voltage-dependent calcium channels, which are essential for regulating the influx of calcium ions into cells during membrane polarization. This auxiliary subunit modulates calcium currents and affects the activation and inactivation kinetics of the channel, thereby playing a key role in cellular processes such as excitation–contraction coupling in muscle and signal transmission in neurons.

In CACNA2D1 knockout mice, there is an observed decrease in calcium channel currents recorded from dorsal root ganglion neurons, chromaffin cells, and cardiomyocytes.

Peripheral nerve injury leads to an increase in alpha-2/delta-1 expression in damaged dorsal root ganglion sensory neurons. Mice overexpressing alpha-2/delta-1 display neuropathic symptoms such as tactile allodynia and hyperalgesia, without nerve injury.