POLK encodes DNA polymerase kappa (Polκ), a Y-family DNA polymerase specialized in translesion synthesis (TLS), enabling DNA replication past DNA lesions when normal high-fidelity polymerases stall 1. Polκ plays dual roles in DNA damage response: it participates in nucleotide excision repair gap-filling after UV-induced lesion excision, and catalyzes TLS to allow replication fork progression through unrepaired damage 1. Mechanistically, Polκ requires recruitment to damage sites through m6A RNA modifications and PCNA interaction, though it lacks 3'-5' proofreading activity, making it error-prone and capable of introducing base substitutions and frameshift mutations 1. Polκ serves as the primary TLS polymerase for aldehyde-induced interstrand crosslinks (ICLs), with its catalytic activity essential for lesion bypass, while displaying non-catalytic roles in cisplatin ICL repair 2. Clinically, impaired Polκ function increases cancer risk due to accumulation of unrepaired lesions 3, while its expression is positively regulated by RIP140 and p53, correlating with improved colorectal cancer survival when POLK levels are low 4. POLK is predominantly expressed in testis, generating multiple transcript isoforms 5. These findings establish Polκ as critical for genome stability maintenance across multiple DNA damage response pathways.