NEK6 is a serine/threonine kinase essential for mitotic cell cycle progression, phosphorylating multiple substrates including KIF11, EML4, and FOXN3 to regulate spindle formation, chromosome 9, and cytokinesis 1. Beyond its canonical mitotic functions, NEK6 plays critical roles in disease pathogenesis. In C9orf72-associated amyotrophic lateral sclerosis/frontotemporal dementia, NEK6 mediates poly(PR)-induced neuronal toxicity through p53-related DNA damage, making it a therapeutic target for neurodegenerative disease 1. In pulmonary fibrosis, NEK6 phosphorylates FOXN3, promoting its degradation and derepressing pro-fibrotic Smad signaling, with inverse FOXN3/Smad4 expression patterns observed in patient tissues 2. In ovarian cancer, NEK6 suppresses FOXO3 nuclear translocation to stabilize c-MYC and promote purine synthesis, driving chemoresistance 3. More broadly, NEK6 is significantly elevated in multiple cancer types and promotes transformation through mechanisms independent of effects on normal cells 4. High NEK6 expression correlates with poor prognosis in ovarian cancer, increased metastasis, and reduced overall survival 5. NEK6 inhibition represents a promising therapeutic strategy across cancers and neurodegenerative diseases.