ATP5ME encodes the membrane subunit e of mitochondrial ATP synthase (Complex V), a key component of the F₀ domain that couples proton translocation across the inner mitochondrial membrane to ATP synthesis 1. The protein functions as part of the proton-transporting ATP synthase complex, which generates ATP from ADP using the proton gradient established by the electron transport chain 1. ATP5ME is part of the membrane domain that links to the soluble catalytic F₁ head via rotating central and stationary peripheral stalks 1. Clinically, ATP5ME expression is dysregulated in multiple disease contexts. It is significantly upregulated in multiple myeloma plasma cells compared to healthy plasma cells, suggesting a role in cancer cell metabolism 2. ATP5ME was identified as a core gene in atherosclerosis and venous thrombosis pathology, where it participates in oxidative phosphorylation and mitochondrial function 3. In cardiac hypertrophy, restoring ATP5ME expression through miRNA inhibition contributes to cardioprotective effects by improving mitochondrial membrane potential and oxidative phosphorylation 4. Additionally, ATP5ME was identified in a genomic deletion associated with recessive retinal degeneration 5, and its downregulation correlates with multidrug resistance in chr4 myeloid leukemia through epigenetic mechanisms 6. ATP5ME overexpression in hepatocellular carcinoma promotes cell proliferation via MAP kinase signaling, making it a potential therapeutic target 7.