NEK9 is a serine/threonine kinase that functions as a pleiotropic regulator of mitotic progression and cell cycle control. Mechanistically, NEK9 phosphorylates histone H3, beta-casein, and the kinases NEK6 and NEK7, releasing their autoinhibitory functions to stimulate activity 123. NEK9 is critical for G1/S transition and S phase progression, controlling spindle dynamics and chromosome 14 during mitosis 234. Beyond cell cycle regulation, NEK9 participates in diverse cellular processes including mTORC1 signaling inhibition through Raptor phosphorylation, metastasis signaling via ROBO1/TRIM28/cortactin pathways, and ciliary proximal segment length determination 567. Disease relevance encompasses both germline and somatic contexts. Biallelic NEK9 mutations cause rare congenital disorders including lethal congenital contracture syndrome 10 and arthrogryposis with gaze palsy 8. In cancer, NEK9 overexpression drives tumorigenesis and chemoresistance across multiple malignancies. NEK9 upregulation promotes gastric cancer metastasis and is associated with worse prognosis in gastric and colon cancers 69. NEK9 mediates docetaxel resistance in oral squamous cell, prostate, and pancreatic cancers 10. Clinically, NEK9 emerges as a therapeutic target; inhibition via fostamatinib or combination strategies with BRD inhibitors shows promise in overcoming chemoresistance 1011.