CACNA2D2 encodes the α2δ-2 subunit of voltage-gated calcium channels, functioning as a regulatory subunit that modulates calcium current density and activation/inactivation kinetics of P/Q-type, N-type, and L-type calcium channels 1. Loss of CACNA2D2 function impairs calcium-dependent neuronal signaling 2, while overexpression can induce apoptosis. Biallelic and de novo CACNA2D2 variants cause developmental and epileptic encephalopathy with cerebellar atrophy as a consistent feature 3. Both gain-of-function and loss-of-function variants are associated with intellectual disability and global developmental delay, with loss-of-function variants producing severe phenotypes 4. In animal models, CACNA2D2 knockout mice exhibit growth retardation, ataxia with cerebellar granule cell apoptosis, seizure susceptibility, and cardiac abnormalities 5. Notably, α2δ-2 knockout increases hippocampal susceptibility to proconvulsant stimuli despite reduced baseline activity 2. Recent therapeutic findings suggest CACNA2D2 represents a disease-modifying target: gabapentinoids binding to α2δ-2 suppress tau oligomer accumulation and neuronal cell death in frontotemporal lobar degeneration-tau models 6. CACNA2D2 also contributes to nicotine-motivated behavior across species 7. The gene has been identified in opsoclonus-myoclonus-ataxia syndrome with severe cerebellar atrophy 8, establishing its broader role in neurological disease.