CDK4 mutations in arginine residue 24 (CDK4R24C) are currently reported in melanoma patients with a familial predisposition and prevent the binding of p16 to the catalytic subunit, triggering constitutive activation of the kinase [22], and conferring a biological behavior similar to p16 loss, as proved by pre-clinical models [25,26]. Here, CDKN2A is linked to melanoma.