ATP5F1A encodes the alpha subunit of mitochondrial ATP synthase complex V (F1F0-ATPase), a critical enzyme that synthesizes ATP from ADP using the proton gradient generated across the inner mitochondrial membrane by the electron transport chain. The protein forms part of the F1 catalytic head domain alongside the beta subunit, with rotation of the central stalk coupling proton translocation to ATP synthesis. Beyond its canonical role, ATP5F1A can bind the bacterial siderophore enterobactin and facilitate mitochondrial iron accumulation. Loss-of-function ATP5F1A variants cause neurodevelopmental disease characterized by developmental delay, motor dysfunction, and movement disorders including dystonia, hereditary spastic paraplegia, and cerebral palsy 12. Zebrafish models of atp5fa1 knockdown display growth retardation and impaired motor neuron development, with dysregulation of autophagy-related genes (apln, becn1, map1lc3b) identified as a potential mechanistic pathway 1. In cancer, aberrant phosphorylation of ATP5F1A by TNK2/ACK1 tyrosine kinase stabilizes complex V and increases mitochondrial energy output to support prostate cancer growth; TNK2 inhibitors can reverse this phosphorylation to induce mitophagy and suppress tumor progression 3. In heart failure, cardiomyocyte-specific overexpression of ATP5F1A improves cardiac function and reduces fibrosis in disease models 4.