CDK2 is a serine/threonine kinase that controls cell cycle progression, particularly at the G1-S transition by interacting with cyclins E and A2 123. While essential for meiosis, CDK2 is dispensable for mitosis 45. CDK2 phosphorylates multiple substrates including RB1, E2F regulators, BRCA2, and NPM1 to drive DNA synthesis initiation and centrosome duplication 67. At mitotic exit, CDK2 activity bifurcates cells into proliferative or quiescent states, controlled by the CDK inhibitor p21 8. CDK2 orchestrates a critical balance between proliferation, apoptosis, and DNA repair, including homologous recombination control via BRCA2 phosphorylation that decreases in S phase when recombination is active 79. Clinically, CDK2 overexpression via cyclin A/E complexes drives uncontrolled cancer cell proliferation 10. CCNE1 amplification-driven CDK2-cyclin E1 hyperactivity represents an emerging therapeutic vulnerability, with selective CDK2 degraders showing promise in resistant breast cancers 11. Sensitivity to CDK2 inhibition depends on P16INK4A and cyclin E1 co-expression, serving as predictive biomarkers 12. CDK2 also regulates neuroinflammation; MEF2C-mediated p21 upregulation suppresses CDK2-dependent RB degradation and NFκB activation in microglia 13. Despite therapeutic potential, no CDK2 inhibitor has achieved FDA approval due to selectivity challenges 10, though highly selective compounds like AZD8421 show promise 14.