CDKN1A (p21) is a cyclin-dependent kinase inhibitor functioning as a critical cell cycle checkpoint regulator and tumor suppressor. Primarily, CDKN1A inhibits CDK4/6 and other cyclin-dependent kinases, blocking phosphorylation of key substrates like RB1 and preventing cell cycle progression through G1/S and G2 phases 1. The gene is directly transcriptionally activated by p53 in response to DNA damage, mediating p53-dependent growth suppression 1. CDKN1A also suppresses DNA synthesis by competing with PCNA-binding partners. Beyond cell cycle control, CDKN1A regulates cellular senescence; RIG-I stabilizes CDKN1A mRNA in aging stem cells, promoting senescence through elevated p21 protein 2. In ovarian aging, FOXP1 declines with age and reciprocally inhibits CDKN1A transcription, suggesting CDKN1A upregulation contributes to oocyte aging 3. Clinically, CDKN1A alterations associate with cancer susceptibility. Genetic polymorphisms (rs1801270) show significant associations with colorectal cancer risk, with AC genotypes potentially protective 4. In gastric adenocarcinomas, CDKN1A exhibits complex epigenetic regulation via histone acetylation, with implications for histone deacetylase inhibitor therapy 5. CDKN1A also promotes cisplatin-induced acute kidney injury through ferroptosis and ROS production 6, and accumulates dose- and LET-dependently after radiation exposure, indicating its role in DNA damage response 7.