RAD18 is an E3 ubiquitin ligase that plays critical roles in DNA damage tolerance and post-replicative repair mechanisms. The protein forms stable complexes with E2-conjugating enzymes UBE2B and UBC13 to mediate PCNA monoubiquitination at lysine-164, which is essential for translesion DNA synthesis 12. RAD18 operates through temporally distinct pathways: in S-phase, it works with UBC13, RAD51, and REV1-POLζ for gap filling, while in G2-phase, it collaborates with REV1 and POLζ translesion synthesis polymerases 1. The protein's function is regulated by O-GlcNAcylation at specific serine and threonine residues, which enhances its accumulation at DNA damage sites and promotes both translesion synthesis and homologous recombination repair 3. Beyond DNA repair, RAD18 exhibits diverse cellular functions, including regulation of interferon signaling by targeting phosphorylated IRF3 for autophagic degradation through K63 polyubiquitination 4. In cancer contexts, RAD18 mediates replication fork recovery in BRCA1-deficient cells through a pathway involving UBC13, PALB2, and RNF168 5. The protein contributes to mutagenesis and carcinogenesis, with RAD18 mutations frequently observed across various human solid tumors 67.