TP53I3 is a p53-inducible NADPH:quinone reductase that functions as a tumor suppressor through dual roles in DNA damage response and apoptosis. As an enzyme, TP53I3 catalyzes NADPH-dependent reduction of quinones, particularly showing strong preference for 1,2-naphthoquinone, with concurrent reactive oxygen species (ROS) generation that triggers p53-dependent apoptosis 1. Functionally, TP53I3 promotes homologous recombination repair following DNA damage 2, while its ROS-generating activity facilitates apoptotic pathways downstream of p53 3. Clinically, TP53I3 demonstrates disease relevance across multiple cancer types. In hereditary ovarian cancer, TP53I3 acts as a BRCA-like tumor suppressor; TP53I3-deficient cells show reduced homologous recombination repair efficiency and increased cisplatin sensitivity 2. In lung adenocarcinoma, elevated TP53I3 correlates with poor prognosis and promotes tumor progression via PI3K/AKT/mTOR pathway activation 4. TP53I3 is also identified as a critical gene in NASH-hepatocellular carcinoma progression 5 and mediates oncolytic viral-induced apoptosis in lung cancer cells 3. Post-radiation exposure, TP53I3 expression becomes dysregulated in immune cells, contributing to late biological effects 6. These findings establish TP53I3 as both a protective tumor suppressor and a potential therapeutic target depending on cancer context.