ATP5F1A encodes the alpha subunit of mitochondrial ATP synthase complex V, which catalyzes ATP synthesis from ADP using the proton gradient generated by the respiratory chain 1. The protein forms the catalytic core of the F1 domain together with the beta subunit (ATP5F1B), though ATP5F1A itself does not contain the high-affinity ATP-binding sites 2. ATP5F1A function is regulated by post-translational modifications including tyrosine phosphorylation at residues Y243 and Y246 by TNK2/ACK1 kinase, which prevents binding to the inhibitor ATP5IF1 and enhances ATP synthase activity in cancer cells 3. Lactylation at K531, regulated by SIRT3, impairs ATP synthase activity and increases reactive oxygen species generation 4. Disease-causing mutations in ATP5F1A result in mitochondrial complex V deficiency with variable neurologic phenotypes including developmental delay, motor dysfunction, hypotonia, epilepsy, and dystonia 15. Functional studies in zebrafish demonstrate that ATP5F1A deficiency causes growth retardation, motor neuron defects, and dysregulated autophagy pathways 5. The protein is also involved in mitochondrial quality control pathways and can be released extracellularly as part of alternative mitochondrial clearance mechanisms 6. These findings establish ATP5F1A as essential for cellular energy metabolism and highlight its clinical significance in mitochondrial disorders.