In summary, these three publications thus uncover the molecular mechanism of cyclin D degradation via CRL4AMBRA1, establish AMBRA1 as a relevant tumor suppressor gene and sensitivity factor for CDK4/6 inhibition and provide hypotheses for therapeutic vulnerabilities of AMBRA1-deficient tumors by CDK2/4/6 or CHK1 inhibition with AMBRA1 loss also serving as predictive biomarker.1–3. The gene discussed is CDK4; the disease is neoplasm.