The cyclin-dependent kinase 4 inhibitor A (CDK4I or p16-INK4) acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6 and by subsequently inhibiting their interaction with cyclins D and retinoblastoma protein phosphorylation. Defects in p16-INK4 are involved in tumor formation in a wide range of tissues. These defects cause cutaneous malignant melanoma 2 (CMM2), familial atypical multiple mole melanoma-pancreatic carcinoma syndrome, melanoma-astrocytoma syndrome and Li-Fraumeni syndrome.