TP53 and cancer: Future studies will clinically anchor our discoveries by: (1) formally assessing tumour‐initiating potential of pre‐malignant cells through transplantation and genetic lineage‐tracing; (2) validating p53‐dependent RPG‐regulating TFs in human datasets to identify therapeutically viable targets for pharmacological testing; (3) leveraging lineage‐specific gene perturbations for synthetic lethal targeting in defined p53‐deficient cancers, with target prioritisation informed by computational evaluation.