APLF (aprataxin and PNKP-like factor) is a multifunctional DNA repair protein and histone chaperone essential for maintaining genomic stability. Primarily, APLF functions as a poly(ADP-ribose)-binding protein recruited to DNA damage sites through interaction with branched poly-ADP-ribose chains via its tandem PBZ domains 1, where tyrosine and basic residues recognize ADP-ribose moieties 1. At damage sites, APLF acts as a histone chaperone mediating histone eviction and recruiting the MACROH2A1 variant 23. APLF possesses nuclease activities including AP endonuclease and 3'-5' exonuclease functions that process damaged DNA 4. The protein facilitates both single-strand break repair and non-homologous end-joining (NHEJ) through FHA domain-dependent interactions with XRCC1 and XRCC4-DNA ligase IV 56. Following ionizing radiation, ATM phosphorylates APLF at serine-116 in a PARP3-dependent manner, enhancing its recruitment to damage sites and DSB repair efficiency 7. Recently discovered functions include facilitating interstrand DNA crosslink repair and replication fork protection through PARP1-mediated recruitment, contributing to cisplatin resistance in cancer cells 8. Additionally, nuclear localization of APLF promotes epithelial-mesenchymal transition and breast cancer metastasis 9. These multifaceted roles establish APLF as a critical coordinator of DNA damage responses with implications for both normal DNA repair and cancer chemoresistance.