NEK3, a member of the NIMA-related kinase family, is involved in multiple biological processes. It has been associated with neuronal function, cell cycle-related activities, and cytoskeletal regulation. In the context of cell signaling pathways, it participates in prolactin-mediated signaling in breast cancer cells [1,2].

In breast cancer, overexpression of Nek3 potentiates prolactin-mediated cytoskeletal reorganization, cell migration, and invasion. Down-regulation of Nek3 expression by siRNA attenuates these processes [2]. In gastric cancer, NEK3 is overexpressed, which is significantly correlated with pT stage, pathologic TNM stage, lymph node metastasis, and poor prognosis. It may serve as a prognostic biomarker and potential therapeutic target [3]. Biallelic loss-of-function NEK3 mutations in humans are associated with abnormal cardiac left-right patterning through SIRT2-mediated α-tubulin deacetylation and down-regulation of inner ring nucleoporins, suggesting it could be a candidate gene for human ciliopathies [4]. In neurons, Nek3 influences neuronal morphogenesis and polarity through effects on microtubules, with unphosphorylated Nek3 causing microtubule deacetylation [5].

In conclusion, NEK3 plays crucial roles in cell migration, proliferation, and in maintaining normal cellular and organ functions. Its dysregulation is associated with diseases such as breast and gastric cancer, as well as cilia-related disorders. Studies on NEK3, especially through loss-of-function models, have provided valuable insights into its functions and its implications in disease, which may guide the development of targeted therapies.