P21, one of the most CKIs, is important checkpoints of P53 signaling pathway for G1/S transition by inhibiting the activity of kinases such as CyclinD/CDK4, CyclinD/CDK6 and CyclinE/CDK2 [48, 49], which plays multiple roles in inhibition cell proliferation in normal and cancer cells and was almost downregulated in many types of cancer. The gene discussed is CDK4; the disease is cancer.