Using cell cycle mapping on human MASH liver tissues, we identified the molecular factors that drive pathological endocycling (Wee1, CDK2, and RAIDD), providing new therapeutic targets for pre-clinical investigation.<h4>Conclusions and implications</h4>This application illustrates how cell cycle mapping can uncover key proteins that drive disease-associated cell state transitions and broaden the scope of LHETs from therapy resistance to cancer prevention. This evidence concerns the gene CRADD and cancer.