CACNA1C encodes the pore-forming α1C subunit of the CaV1.2 L-type voltage-gated calcium channel, a critical regulator of membrane physiology in heart, brain, and immune tissues 1. The channel mediates calcium ion transmembrane transport and regulates cardiac conduction, ventricular action potentials, and neuronal excitability essential for synaptic plasticity and neurotransmitter release 2. CaV1.2 also functions in non-excitable immune cells including microglia and peripheral immune cells, where it modulates activation and cytokine release 2. Additionally, CACNA1C may act as a receptor for influenza virus entry when sialylated on lung tissues 3. Mutations in CACNA1C cause multisystem channelopathies ranging from severe Timothy syndrome—characterized by neurodevelopmental deficits, long-QT arrhythmias, and immune dysfunction 1—to isolated neurological manifestations including developmental delay, intellectual disability, autism, epilepsy, and hypotonia 4. Both gain-of-function and loss-of-function variants contribute to disease, with gain-of-function mutations typically producing more severe phenotypes 5. CACNA1C variants are associated with schizophrenia, bipolar disorder, and autism spectrum disorder, with pathway analysis supporting pleiotropic effects of calcium channel signaling on multiple psychiatric conditions 67. Emerging therapeutic approaches, including antisense oligonucleotides targeting pathogenic exon splicing, show promise in reversing disease-relevant neurophysiology 8.