NME8 (NME/NM23 family member 8) is a multifunctional protein with distinct enzymatic activities and roles in cellular processes. Unlike other NME family members, NME8 lacks nucleoside diphosphate kinase activity but possesses intrinsic kinase activity and 3'-5'-DNA exonuclease activity that processes single-stranded DNA substrates and removes mismatched 3' termini from double-stranded DNA 1. NME8 is essential for male reproductive health, particularly in protecting against chemotherapy-induced testicular damage through antioxidant mechanisms, autophagy activation, and DNA damage prevention 2. The protein shows nuclear translocation under cellular stress and may function in DNA repair processes 2. Disease-wise, NME8 genetic variants (rs2718058) are associated with late-onset Alzheimer's disease risk in certain populations and correlate with neuroimaging biomarkers and cognitive decline 34. Additionally, NME8 overexpression promotes renal cell carcinoma metastasis through JAK/STAT pathway activation and epithelial-mesenchymal transition 5. The gene is also implicated in ciliary dysfunction associated with idiopathic normal pressure hydrocephalus 6. These diverse roles highlight NME8's importance in DNA metabolism, reproductive biology, neurodegeneration, and cancer progression.