CACNA2D3 encodes the alpha-2/delta-3 auxiliary subunit of voltage-gated calcium channels, regulating calcium current density and activation/inactivation kinetics of P/Q-type, N-type, and L-type channels. Beyond its canonical role in calcium signaling, CACNA2D3 functions as a tumor suppressor across multiple cancer types. In gastric cancer, CACNA2D3 methylation occurs in 30% of cases and correlates with significantly shorter survival in advanced disease 1. Similarly, downregulation via loss of heterozygosity and epigenetic silencing in nasopharyngeal carcinoma promotes cell proliferation, invasion, and epithelial-to-mesenchymal transition; restoration of CACNA2D3 increases intracellular calcium to induce mitochondrial apoptosis and antagonize Wnt signaling 2. In gliomas, CACNA2D3 downregulation correlates with poor survival, and ectopic expression inhibits proliferation and tumor growth in vivo 3. CACNA2D3 also shows involvement in neurological conditions: loss-of-function studies in C. elegans validate it as a conserved autism-associated gene affecting GABAergic neuron remodeling 4, and recent evidence suggests roles in nicotine-motivated behavior 5. Clinically, multiple agents targeting calcium channel alpha-2/delta subunits—including pregabalin and gabapentin—are approved for chr3 pain, anxiety, and epilepsy, conditions associated with CACNA2D3 dysfunction.