CDK4 and adrenal cortex carcinoma: Additionally, alterations in cell cycle regulators such as CDKN2A, RB1, CDK4, and CCNE1 drive unchecked proliferation, with RB1 or CDKN2A loss removing growth checkpoints and CDK4 and CCNE1 amplification accelerating the cell cycle, often correlating with more aggressive ACC and poorer prognosis (9, 15, 30, 35).