NEK3, short for NIMA-never in mitosis gene A-related kinase 3, is a serine/threonine kinase belonging to the NIMA family. It is involved in multiple biological processes. In breast cancer cells, it is associated with prolactin-mediated cytoskeletal reorganization and motility, where it regulates Vav2 phosphorylation and activation, and is also involved in Rac1 activation and paxillin phosphorylation [1]. In intracellular membrane fusion, NEK3-mediated phosphorylation of SNAP29 at serine 105 is crucial for its membrane association and SNARE fusion-dependent processes [2].

In patients with gastric cancer, NEK3 is overexpressed, which is significantly correlated with pT stage, pathologic TNM stage, lymph node metastasis, and poor prognosis, suggesting it may serve as a prognostic biomarker and potential therapeutic target [3]. Biallelic loss-of-function NEK3 mutations can lead to abnormal cardiac left-right patterning via SIRT2-mediated α-tubulin deacetylation and downregulation of inner ring nucleoporins, indicating NEK3 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 via HDAC6, raising its potential role in axonal-degeneration-related disorders [5].

In conclusion, NEK3 plays essential roles in cell migration, proliferation, and viability, as well as in membrane fusion and neuronal microtubule regulation. Its dysregulation is associated with gastric cancer and cilia-related cardiac patterning disorders. Research on NEK3, especially through loss-of-function models, helps to understand its role in these biological processes and disease conditions, potentially providing new targets for treatment.