While the absence of p16Ink4a, an inhibitor of cyclin-dependent kinases 4/6 (CDK4/6)-mediated phosphorylation of pRb, abrogates the G1/S cell-cycle arrest and promotes aberrant proliferation, functional loss of p14Arf, a central negative regulator of mouse double minute 2 homolog (MDM2), suppresses apoptosis by escape from p53-mediated anti-tumor surveillance (Figure 1B). The gene discussed is CDKN2A; the disease is neoplasm.