BARD1 (BRCA1-associated RING domain 1) encodes an E3 ubiquitin-protein ligase that functions as a tumor suppressor through its heterodimeric complex with BRCA1 1. The BRCA1-BARD1 complex mediates formation of Lys-6-linked polyubiquitin chains and coordinates DNA damage repair, ubiquitination, and transcriptional regulation to maintain genomic stability 2. Mechanistically, BARD1 plays a critical role in homologous recombination (HR) by promoting DNA end resection through direct interactions with nucleases EXO1, BLM, and WRN 3. BRCA1-BARD1 also enhances RAD51 recombinase activity and promotes assembly of synaptic complexes essential for DNA joint formation 2. Germline BARD1 variants are associated with inherited cancer susceptibility, particularly in breast and ovarian cancers, though disease penetrance is gene-specific 4. Functional studies demonstrate that HDR-deficient BARD1 missense variants, particularly in the ankyrin repeat and BRCT domains, correlate with increased DNA damage sensitivity and cancer risk 5. BARD1 also functions with CSTF1 to modulate mRNA processing and RNA polymerase II stability. Loss of BARD1 function impairs the balance between homologous recombination and non-homologous end joining repair pathway choice 6, with therapeutic implications for understanding PARP inhibitor resistance.