PALB2 (partner and localizer of BRCA2) serves as a critical scaffold protein in homologous recombination DNA repair by forming the essential BRCA1-PALB2-BRCA2 complex 1. The protein recruits BRCA2 and RAD51 to DNA breaks, stimulates RAD51's strand-invasion activity, and helps overcome inhibitory effects of replication protein A 1. PALB2 functions through both BRCA1-dependent and BRCA1-independent recruitment mechanisms, ensuring efficient DNA double-strand break repair even when BRCA1 is compromised 1. Germline truncating mutations in PALB2 confer significant breast cancer risk, with odds ratios of 4.69 compared to controls 2. The lifetime breast cancer risk for PALB2 mutation carriers is substantial, estimated at 14% by age 50 and 35% by age 70, with risks potentially overlapping those of BRCA2 carriers 3. PALB2 mutations also increase contralateral breast cancer risk, particularly in carriers with estrogen receptor-negative tumors who show a hazard ratio of 2.9 4. The protein is found in colorectal cancer patients at a frequency of approximately 0.2% 5, demonstrating its broader role in cancer predisposition beyond breast cancer.