NEK4

NEK4 (NIMA-related kinase 4) is a serine/threonine protein kinase within the NEK family that contributes to the maintenance of cellular homeostasis through functions linked to cell-cycle regulation, primary cilia biology, and the DNA damage response (DDR)^[1][2]. Mechanistically, NEK4 has been associated with cellular responses to double-stranded DNA damage and participates in pathways that preserve genomic stability, placing this kinase at the interface between cell-cycle control and DNA repair processes^[1][3]. Evidence further indicates that NEK4 contributes to non-homologous end joining (NHEJ) through recruitment of DNA-dependent protein kinase (DNA-PK) to DNA-damage foci, supporting efficient repair of DNA double-strand breaks^[1]. Beyond genome maintenance, NEK4 is linked to cilium integrity, microtubule stabilization, and primary cilia function, highlighting a functional connection between ciliogenesis and stress-response pathways^[2][4]. In disease-related contexts, altered NEK4 activity has been associated with ciliopathy-relevant phenotypes, while dysregulated expression has been reported in several tumor types, supporting continued investigation of NEK4 in cancer and genomic-instability models^[3][5]. Compared with related NEK family members, NEK4 remains relatively understudied, yet available evidence identifies two major isoforms, NEK4.1 and NEK4.2, which display distinct interaction profiles and differential effects on RNA-splicing regulation, indicating isoform-specific biological functions^[4][5]. For experimental applications, NEK4 is frequently investigated in DDR, ciliogenesis, microtubule-dynamics, and senescence models, whereas selective NEK4-targeted pharmacological modulators remain limited in the current literature^[1][3].