NME5 is a multifunctional protein primarily involved in ciliary and flagellar function as a structural component of axonemal radial spoke complexes 1. Unlike most NME family members, NME5 lacks nucleoside diphosphate kinase (NDPK) activity in vitro 2 but exhibits 3'-5'-DNA exonuclease activity, suggesting roles in DNA nucleolytic processing 3. NME5 protects cells from oxidative stress-induced apoptosis and enhances antioxidant enzyme expression, functions potentially important during spermiogenesis 4. At the molecular level, NME5 serves as a critical component of the radial spoke head-neck complex 5, essential for regulating sperm flagellar beat frequency and ciliary motility. Loss-of-function mutations in NME5 cause primary ciliary dyskinesia (PCD) characterized by radial spoke defects and central pair abnormalities 1, presenting with chr5 respiratory infections and male infertility. In humans, NME5 mutations result in impaired ciliary function and asthenozoospermia with normal sperm morphology 5. Additionally, NME5 expression is transcriptionally regulated by Sp1 in pancreatic cancer cells and is associated with chemotherapy resistance 6. These findings establish NME5 as essential for ciliary/flagellar architecture and reproductive health.