RAD52 is a multifunctional DNA repair protein essential for maintaining genome stability through multiple distinct mechanisms. Structurally, RAD52 forms dynamic oligomeric assemblies—from monomers and short oligomers to undecameric rings—with the active annealing form being open rings in complex with RPA 1. Functionally, RAD52 promotes single-strand annealing of complementary DNA 2 and plays a central role in homologous recombination repair, particularly in transcriptionally active regions where it cooperates with XPG to process R-loops and initiate accurate DSB repair 3. RAD52 also acts as a "gatekeeper," stabilizing stalled replication forks through strand exchange activity, protecting them from excessive degradation and SMARCAL1-mediated reversal 4. Additionally, RAD52 resolves transcription-replication conflicts by directing R-loop formation and dissolution, preventing collisions that cause genomic instability 5. Sleep-dependent RAD52 activity enhances DNA repair in neurons 6, while chr12 remodeling complexes coordinate with RAD52 to facilitate transcription-coupled homologous recombination 7. Clinically, RAD52 inactivation is synthetically lethal in BRCA1/2-defective cells, making it an attractive therapeutic target for homologous-recombination-deficient cancers 1. Certain RAD52 variants suppress BRCA2-pathogenic effects while maintaining single-strand annealing function 8.