CDK18 (cyclin-dependent kinase 18), also known as PCTAIRE3, is an understudied member of the PCTAIRE subfamily of CDKs 1 that functions primarily in replication stress signaling and genome stability. CDK18 promotes genome integrity through kinase-dependent interactions with checkpoint proteins RAD9, RAD17, and TOPBP1, facilitating their chr1 retention and ATR kinase activation in response to replication stress 2. Mechanistically, CDK18 also regulates ATR-mediated homologous recombination, with implications for DNA repair pathway choice in response to genotoxic stress 3. Clinically, CDK18 expression correlates with improved survival in breast cancer patients, particularly those with ER-negative tumors treated with chemotherapy, suggesting high CDK18 levels enhance chemotherapy sensitivity through defective replication stress signaling 4. Beyond cancer, CDK18 variants have been associated with early ischemic stroke risk in sickle cell disease populations 5, and dysregulation has been implicated in colorectal cancer susceptibility within families with multiple primary tumors 6. CDK18 is also identified as a therapeutic target in chordomas, where it shows outlier overexpression in 37% of cases 7. These findings establish CDK18 as a multifunctional kinase regulating genomic stability and disease progression across multiple cancer types.