ADCY5 encodes adenylyl cyclase 5, an enzyme that catalyzes cAMP formation in response to G-protein coupled receptor signaling 123. The protein mediates downstream signaling from β1-adrenergic receptors and regulates cytosolic calcium increases in response to elevated blood glucose, contributing to calcium-dependent insulin secretion 24. ADCY5 is the predominant adenylyl cyclase isoform in striatal medium spiny neurons, where it integrates dopaminergic signaling and controls movement initiation and inhibition of involuntary movements 5. ADCY5 mutations cause a spectrum of hyperkinetic movement disorders characterized by chorea, myoclonus, and/or dystonia, often with paroxysmal exacerbations, developmental delay, and intellectual disability 56. Gain-of-function mutations dysregulate the cAMP pathway, reducing inhibitory striatal activity and triggering involuntary movements 5. These mutations are classified as benign hereditary chorea alongside NKX2-1, GNAO1, and PDE10A mutations 78. Genetic variants in ADCY5 associate with type 2 diabetes risk and elevated fasting glucose 9, though adipose tissue ADCY5 expression correlates with obesity rather than impaired glucose metabolism 10. ADCY5 may also participate in mechanisms uncoupling excess adiposity from cardiometabolic complications through insulin-glucose signaling regulation 11.