CKS2 (cyclin-dependent kinase subunit 2) is a regulatory protein essential for cyclin-dependent kinase function and cell cycle progression 1. It binds to CDK catalytic subunits and participates in the SCF ubiquitin ligase complex, facilitating protein degradation through ubiquitin-mediated pathways 2. In cancer biology, CKS2 is aberrantly upregulated across multiple tumor types and promotes malignant progression through multiple mechanisms 3. It enhances cell proliferation, invasion, and migration while suppressing apoptosis by regulating critical genes including p53, CDK1, cyclins A/B1, and caspases 1. CKS2 modulates the PI3K/Akt signaling pathway and promotes ferroptosis resistance through glutathione metabolic reprogramming 4. Additionally, E2F1 transcriptionally activates CKS2, which subsequently suppresses PTEN expression to sustain proliferative signaling 5. Clinically, elevated CKS2 expression strongly correlates with poor prognosis across malignancies 6. Meta-analysis demonstrated that high CKS2 expression associates with reduced overall survival (HR=2.27), advanced tumor stage, lymph node metastasis, and larger tumor size 6. CKS2 serves as an independent prognostic factor in colorectal cancer and is dysregulated through epigenetic mechanisms involving miR-26a and YB-1 17. CKS2 knockdown sensitizes cancer cells to chemotherapy and ferroptosis-inducing agents, positioning it as a promising therapeutic target 4.