Isoform 2 of Voltage-dependent calcium channel subunit alpha-2/delta-1

CACNA2D1 encodes the alpha-2/delta-1 subunit of voltage-dependent calcium channels, an auxiliary protein that modulates calcium channel function and trafficking in the nervous system (UniProt: P54289-2). This subunit is broadly expressed in neural tissue and plays roles in neurotransmitter release and synaptic plasticity through its interaction with calcium channel pore-forming subunits.

The alpha-2/delta-1 subunit is implicated in neurological function, and CACNA2D1 variants have been associated with neurodevelopmental and neuropsychiatric phenotypes. The protein localizes to multiple subcellular compartments, including synaptic membranes and presynaptic terminals, where it influences excitatory and inhibitory neurotransmission.

In Alzheimer's Disease, isoform 2 of CACNA2D1 is significantly downregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2FC: −0.567; Chaparral AD proteomics). This reduction was detected across subcellular fractions in TMT-labeled proteomics experiments, suggesting potential dysfunction in calcium signaling and synaptic transmission as a component of AD pathophysiology.