DNA repair protein Ku80

XRCC5 encodes Ku80, a DNA-binding protein essential for repairing double-strand breaks through the non-homologous end joining (NHEJ) pathway (UniProt: P13010). The protein forms a heterodimer with XRCC6 (Ku70) that binds broken DNA ends and recruits repair machinery to facilitate religation. Beyond its canonical repair role, Ku80 contributes to telomere maintenance, transcriptional regulation as a cofactor, innate immune signaling via the HDP-RNP complex, and ribosomal RNA biogenesis through RNA binding.

No curated disease associations are listed in UniProt for XRCC5. However, proteomics evidence from post-mortem Alzheimer's disease brain tissue shows that Ku80 is significantly down-regulated compared to age-matched controls (Chaparral AD proteomics). The mean log2 fold-change was −1.70 across a single subcellular fraction in TMT-labeled proteomics data, suggesting reduced DNA repair capacity in AD pathology. This decreased expression may reflect impaired DNA damage response mechanisms in diseased tissue.