AK4 (adenylate kinase 4) is a mitochondrial nucleoside phosphate kinase that maintains cellular nucleotide homeostasis through nucleoside-phosphate interconversions 1234. The enzyme preferentially catalyzes AMP phosphorylation using ATP as phosphate donor to produce ADP, and can also phosphorylate CMP, dAMP, and dCMP using GTP as an alternate donor 23. AK4 exhibits diphosphate kinase activity, producing various nucleoside triphosphates from corresponding diphosphate substrates 3. The protein regulates cellular ATP levels by controlling AMPK phosphorylation and activation 45. AK4 plays protective roles in oxidative stress responses 675 and modulates mitochondrial activity by affecting oxygen consumption and TCA cycle intermediates 5. Clinically, AK4 is implicated in various cancers where it promotes metastasis, chemoresistance, and tumor progression through mechanisms involving HIF-1α stabilization and epithelial-to-mesenchymal transition 8910. AK4 expression correlates with poor prognosis in multiple cancer types and represents a potential therapeutic target 511.