KIF18A is a microtubule-depolymerizing kinesin that regulates chromosome 11 and mitotic spindle dynamics during cell division. 1 KIF18A functions as a molecular motor protein that controls microtubule length by suppressing plus-end dynamics, with its activity regulated by HURP through both activation at low concentrations and inhibition through steric exclusion at higher concentrations. 2 The protein's enzymatic activity depends on ATP hydrolysis and involves translocation across the mitotic spindle to achieve chromosome 11. 3 In normal diploid cells, KIF18A is largely dispensable for accurate chromosome 11; 3 however, it becomes essential for cells with whole-genome doubling or chr11 instability (CIN). 4 KIF18A loss induces notable mitotic errors and impaired viability specifically in these genetically unstable cells, creating a therapeutic vulnerability. 3 Clinically, KIF18A is upregulated in 27 of 33 cancers examined and correlates with poor prognosis in liver cancer, pancreatic cancer, lung adenocarcinoma, and glioblastoma. 5 Recent pharmacological studies demonstrate that selective KIF18A inhibitors (such as VLS-1272) selectively kill chr11 unstable cancer cells while sparing normal tissue, with robust anti-tumor effects observed in ovarian cancer and triple-negative breast cancer models at well-tolerated doses. 62 Additionally, KIF18A mutations have been identified in infertile patients with oocyte defects. 7