NEK1

NIMA-related kinase 1 (NEK1) is a serine/threonine kinase that regulates cell cycle progression, ciliogenesis, and DNA repair^[1][2]. Mechanistically, NEK1 phosphorylates α-tubulin and importin-β1 to maintain microtubule homeostasis and nuclear import in motor neurons^[1]. NEK1 also modulates the localization and phosphorylation of α-adducin (ADD1) and Myosin X (MYO10) during meiosis, ensuring proper spindle assembly and chromosome congression^[3]. In DNA damage response, NEK1 acts upstream of ATR and Chk1, facilitating checkpoint control independently of ATM and ATR activity^[4][5]. NEK1 interacts with C21ORF2 through its C-terminal interaction domain, a complex essential for ciliogenesis and homologous recombination, and pathogenic mutations disrupt this association^[6]. Compared with related NEK isoforms, NEK1 uniquely integrates microtubule regulation, ciliary function, and DNA repair, which underscores its pleiotropic cellular roles^[7][8]. Experimental inhibition of NEK1 with kinase inhibitors or genetic knockdown impairs DNA repair, ciliary function, and microtubule stability, while stabilization of microtubules or HDAC6 inhibition can rescue these defects in ALS and iPSC-derived models^[1][9]. Structural characterization of the NEK1 kinase domain provides a framework for designing selective inhibitors for cancer and neurodegenerative disease research^[2]. These studies establish NEK1 as a critical target for functional interrogation of cell cycle regulation, neurodegeneration, and DNA damage repair pathways^[10].