PARP2 is a poly(ADP-ribose) polymerase that catalyzes ADP-ribosylation of proteins and DNA, playing a critical role in DNA repair 12. PARP2 transfers ADP-ribosyl groups from NAD+ to glutamate, aspartate, or serine residues, forming poly(ADP-ribose) chains averaging 20-30 units in length 23. Upon DNA damage, serine ADP-ribosylation becomes the primary form of PARP2-mediated modification, especially when PARP2 interacts with HPF1, which directs serine specificity while limiting chain length 456. PARP2 initiates double-strand break repair by recognizing DNA breaks, recruiting HPF1, and catalyzing histone ADP-ribosylation to promote chr14 decompaction and repair factor recruitment 45. PARP2 uniquely mediates branched poly(ADP-ribose) formation and can ADP-ribosylate DNA at 5'-phosphorylated nicks 37. Beyond DNA damage responses, PARP2 modulates lipid metabolism and serves as a therapeutic target 8. PARP inhibitors trap PARP2 at damaged DNA, creating cytotoxic complexes more lethal than unrepaired breaks 9. However, catalytic inactivation of PARP2 impairs replication-fork progression in rapidly dividing erythroblasts, explaining PARP inhibitor-associated anemia 10.