CACNG8 encodes TARP γ-8, a transmembrane AMPA receptor regulatory protein that serves dual roles in synaptic transmission and cardiac function. As an auxiliary subunit, CACNG8 regulates AMPA receptor (AMPAR) trafficking, gating, and synaptic localization by stabilizing specific receptor conformations 1. Structurally, TARP γ-8's large β1 loop selectively engages ligand-binding domains to modulate gating kinetics, slowing activation, deactivation, and desensitization rates while promoting resensitization 1. CACNG8 also regulates L-type calcium channel activity, though its precise cardiac mechanisms require further characterization. Genetically, CACNG8 variants associate with multiple neuropsychiatric and neurodevelopmental disorders. CACNG8 knockout mice exhibit ADHD-like phenotypes including hyperactivity, impulsivity, and cognitive deficits, with human SNP analysis confirming associations with ADHD susceptibility 2. The SNP rs10420324G reduces CACNG8 transcription and correlates with antisocial personality disorder risk; knockout mice display aggression and impulsivity paralleling ASPD features 3. In cardiac disease, CACNG8 downregulation in dilated cardiomyopathy patients inversely correlates with left ventricular ejection fraction (r = -0.78) 4. Additionally, rare CACNG8 variants may modify inherited retinal dystrophy susceptibility through disrupted postsynaptic AMPAR complex assembly 5. These findings establish CACNG8 as a critical regulator of glutamatergic neurotransmission with pleiotropic effects on neural and cardiac function.