NBN (nibrin) is a critical component of the MRN complex, which orchestrates DNA double-strand break (DSB) repair and genomic stability 1. As a protein-protein adapter within the MRN complex, NBN recognizes phosphorylated proteins and recruits them to DNA damage sites, facilitating the assembly of repair machinery including MRE11 and RAD50 2. The MRN complex initiates homologous recombination repair by mediating DNA end resection and recruiting damage-response kinases (ATM, ATR) to activate cell cycle checkpoints 1. NBN also regulates telomere maintenance through interactions with TERF2, balancing different repair pathways (non-homologous end joining versus microhomology-mediated end-joining) depending on its phosphorylation status 3. Beyond classical DSB repair, the MRN complex liberates cGAS from nucleosome inhibition, enabling innate immune activation and tumor suppression through necroptosis 1. Functionally, cells expressing NBN truncating variants show heightened sensitivity to ionizing radiation and impaired DNA damage signaling 3. Clinically, heterozygous NBN pathogenic variants confer increased cancer susceptibility, particularly for melanoma, pancreatic, prostate, and hematological malignancies, while biallelic mutations cause Nijmegen breakage syndrome 4. These findings establish NBN as a pan-cancer susceptibility gene requiring personalized clinical risk assessment 3.