NME6 is a mitochondrial nucleoside diphosphate kinase that catalyzes phosphoryl transfer from ATP to nucleoside diphosphates via a phosphohistidine intermediate 1. Unlike other NME family members, NME6 monomers are catalytically inactive; the protein gains nucleoside diphosphate kinase activity through heterodimeric interaction with the mitochondrial protein RCC1L, bypassing the need for hexamer assembly 2. Within mitochondria, NME6 regulates nucleotide homeostasis by supplying pyrimidine ribonucleoside triphosphates for transcription and supporting mitochondrial DNA maintenance when cytosolic pyrimidine deoxyribonucleoside triphosphate import is limited. NME6 also participates in mitoribosome biogenesis and modulation of mitochondrial RNA levels. In cancer contexts, NME6 expression correlates with clinical outcome. In lung adenocarcinoma, elevated NME6 is associated with inferior overall survival and links to tumor-infiltrating immune cells and m6A modification pathways 3. Conversely, in ovarian cancer, high NME6 expression in epithelial cells emerges as a protective factor, negatively correlating with immune dysfunction 4. In hepatocellular carcinoma, NME6 participates in a competing endogenous RNA network involving the pseudogene BMS1P8 and miR-30c-2-3p that stratifies patient prognosis 5. At the population level, Mendelian randomization analysis implicates NME6 expression in blood as a genetic contributor to systolic and diastolic blood pressure variation 6.