More than half of chordoma patients exhibit inactivation of the tumor suppressor p16 (cyclin-dependent kinase inhibitor 2a, encoded by CDKN2A), leading to constitutive activation of the cyclin D-cyclin-dependent kinase 4/6 (CDK4/6)-retinoblastoma (RB) pathway,13,14 which may represent an opportunity for therapeutic intervention. Here, CDK4 is linked to chordoma.