While the canonical cyclin D-CDK4/6-initiated entry mechanism has been extensively characterized in a variety of contexts, the alternate cyclin E-CDK2-initiated entry mechanism has mainly been characterized using knockout models and in cancer, where cells can bypass CDK4/6 inhibition via c-Myc upregulation of cyclin E-CDK2 activity, amplification of cyclin E, or downregulation of CDK2 inhibitors18–25. The gene discussed is CDK2; the disease is cancer.