Figure 9 outlines the basic pathogenic role of CDK4 in PC, where the inactivation of the p16INK4a—an endogenous inhibitor of CDK4/6 encoded by CDK2NA—activates the CDK4/6-cyclinD1 complex resulting in the hyperphosphorylation of RB, release of E2F transcription factors and uncontrolled cell proliferation. Here, RB1 is linked to pachyonychia congenita.