ATP8 encodes subunit 8 of mitochondrial ATP synthase (Complex V), which is essential for ATP production from ADP using the proton gradient generated by the electron transport chain 1. The protein is part of the membrane F0 domain of ATP synthase and directly interacts with the ATP synthase complex via ATP8 2. ATP8 plays a crucial role in the assembly, stability, and function of ATP synthase, as demonstrated by studies showing that PRICKLE3, which interacts with ATP8, is necessary for ATPase biogenesis 2. Disease-causing variants in MT-ATP8 are associated with severe mitochondrial disorders including infantile hypertrophic cardiomyopathy and mitochondrial complex V deficiency 3. Clinical manifestations include neurodegeneration, ataxia, developmental delays, and Leigh syndrome, with infantile-onset cases showing significantly worse survival outcomes compared to adult-onset disease 3. The gene is downregulated in heart failure patients with dilated cardiomyopathy, suggesting its involvement in cardiac mitochondrial dysfunction 4. Pathogenic variants lead to reduced ATP synthase function and metabolic abnormalities including elevated lactate and alanine levels 3. Current therapeutic approaches focus on addressing mitochondrial dysfunction, though effective treatments remain limited 5.