CACNA1D encodes the pore-forming α1 subunit of Cav1.3 L-type voltage-gated calcium channels, which mediate calcium ion entry into excitable cells and regulate calcium-dependent processes including muscle contraction, hormone/neurotransmitter release, and gene expression 1. The channel is particularly important in cardiac conduction, sensory perception, and neuronal function [GO annotations provided]. CACNA1D variants have been associated with multiple disease phenotypes. Loss-of-function mutations cause deafness and bradycardia through reduced Cav1.3 activity 1, while gain-of-function de novo variants are linked to neurodevelopmental disorders including autism spectrum disorder and intellectual disability 213. CACNA1D mutations also contribute to congenital hyperinsulinism, causing unregulated insulin secretion and neonatal hypoglycemia 4. Additionally, CACNA1D variants have been identified in familial advanced sleep phase disorder, with altered channel dynamics affecting circadian light entrainment 5. The A749G variant in mice reproduces developmental delay, social deficits, and hyperactivity through altered dopamine neuron excitability 3. Disease-associated variants demonstrate altered channel gating and kinetics, and L-type calcium channel inhibitors like isradipine represent potential therapeutic approaches 1. CACNA1D also serves as a subtype-specific therapeutic target in pancreatic neuroendocrine tumors 6.