CACNA2D3 encodes an auxiliary subunit of voltage-gated calcium channels that regulates calcium current density and channel kinetics 1. The protein functions as a regulatory component for P/Q-type, N-type, and L-type calcium channels, modulating intracellular calcium levels 12. CACNA2D3 serves as a tumor suppressor gene across multiple cancer types. In nasopharyngeal carcinoma, gliomas, and gastric cancer, CACNA2D3 is frequently downregulated through promoter methylation and histone deacetylation 123. CACNA2D3 restoration increases intracellular calcium, triggering mitochondrial-mediated apoptosis and activating the Wnt/Ca²⁺ pathway via NLK upregulation, thereby antagonizing Wnt signaling-driven proliferation, invasion, and epithelial-to-mesenchymal transition 12. CACNA2D3 methylation correlates with poor survival in advanced gastric cancer 3. Beyond oncology, CACNA2D3 is differentially expressed in human pancreatic γ-cells 4, expressed in human brain pericytes but not mouse 5, associates with facial morphology variation 6, and influences nicotine-seeking behavior 7. CACNA2D3 is deregulated in sensory neurons from Fabry disease patients 8. These findings establish CACNA2D3 as a calcium-regulatory tumor suppressor with emerging roles in neuropathology and addiction biology.