NIMA-related kinase 1 (NEK1) (NEK1)

NIMA-related kinase 1 (NEK1) is a multifunctional serine/threonine and tyrosine kinase that serves as a critical regulator of the cell cycle, DNA damage response (DDR), and ciliary function. It is localized to the centrosome, nucleus, and primary cilium, where it coordinates microtubule stability and nucleocytoplasmic transport. Mutations in the NEK1 gene are strongly associated with several human pathologies, most notably amyotrophic lateral sclerosis (ALS), where it is one of the most common genetic risk factors, accounting for 2-3% of cases. In ALS, loss-of-function variants lead to impaired microtubule homeostasis and the formation of toxic protein aggregates. NEK1 is also implicated in polycystic kidney disease (PKD) and various malignancies, where its role in DNA repair makes it a potential target for sensitizing tumors to radiotherapy or chemotherapy. Current drug discovery efforts focus on small-molecule inhibitors like BSc5367 for cancer research and strategies to stabilize microtubules in neurodegenerative contexts.

Other names

ALS24NY-REN-55SRPS2SRPS2ASRTD6OFD2Never in mitosis A-related kinase 1

ATP-competitive inhibition of the kinase domain to block phosphorylation of substrates involved in DNA repair and microtubule stability.