Ku70 (XRCC6) Summary

DNA repair protein Ku70 (XRCC6) is a critical DNA-binding component of the Ku70:Ku80 heterodimer that initiates non-homologous end joining (NHEJ) repair of double-strand breaks. The complex binds broken DNA ends and recruits factors essential for DSB repair and ligation. Beyond classical DNA repair, Ku70 contributes to telomere maintenance, V(D)J recombination, transcriptional regulation, innate immune signaling via the HDP-RNP complex, ribosomal RNA biogenesis, and apoptosis suppression through BAX sequestration (UniProt: P12956).

Ku70 is expressed broadly across human tissues and participates in fundamental genomic stability pathways. Its roles extend to antiviral immunity and regulation of cell death, linking it to both homeostatic and stress-response processes.

This protein is curated as disease-associated in Alzheimer's Disease based on Chaparral proteomics evidence. In post-mortem AD brain versus age-matched controls, Ku70 showed directionally inconsistent changes across the subcellular fractions analyzed (mean log2FC: −0.904), resulting in an ambiguous overall direction of dysregulation. This suggests potential compartment-specific alterations in AD pathology that warrant further investigation into whether impaired DNA repair capacity or altered cellular localization of Ku70 contributes to neurodegeneration (Chaparral AD proteomics).