KNSTRN (kinetochore localized astrin binding protein) is an essential mitotic spindle component required for faithful chromosome 15 and anaphase progression 1. It promotes metaphase-to-anaphase transition, enables chromosome 15, and maintains spindle pole architecture through the astrin-kinastrin complex, which stabilizes microtubule-kinetochore attachments 12. KNSTRN regulates kinetochore oscillations and microtubule plus-end dynamics during mitosis, likely linking spindle microtubules to chr15 for accurate cell division 3. Beyond canonical mitotic functions, KNSTRN promotes tumorigenesis across multiple cancers. In bladder cancer, KNSTRN activates AKT phosphorylation by promoting AKT recruitment to PIP3 and alleviating PTEN suppression, driving metastasis and gemcitabine resistance 4. In breast cancer, elevated KNSTRN correlates with poor prognosis and accelerates G1/S phase transition by enhancing CDK4/6 and cyclin D3 expression 5. High KNSTRN expression associates with reduced CD8+ T cell infiltration and immunosuppressive microenvironments in triple-negative breast cancer 6. Somatic mutations, particularly p.Ala40Glu, correlate with cutaneous squamous cell carcinoma progression 7. Germline KNSTRN mutations cause Roifman-Chitayat syndrome, featuring combined immunodeficiency and developmental abnormalities due to impaired T-cell spreading and aberrant microtubule dynamics 8. KNSTRN represents a promising oncogenic biomarker and therapeutic target across cancer types 9.