While the detailed mechanisms behind IRES-mediated p53 synthesis and the link between defective p53 mRNA translation and tumorigenesis still remain to be further elucidated, the discovery of the regulatory proteins of p53 IRES and their defective expression in cancer cells has opened the door for exploring novel biomarkers for cancer diagnosis and new therapeutic avenues for reactivating p53 in cancer cells. The gene discussed is TP53; the disease is cancer.