{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:21:42Z","timestamp":1790720502400,"version":"4.1.0"},"reference-count":217,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T00:00:00Z","timestamp":1641427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R15CA243109-01"],"award-info":[{"award-number":["1R15CA243109-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cell cycle kinases represent an important component of the cell machinery that controls signal transduction involved in cell proliferation, growth, and differentiation. Nek2 is a mitotic Ser\/Thr kinase that localizes predominantly to centrosomes and kinetochores and orchestrates centrosome disjunction and faithful chromosomal segregation. Its activity is tightly regulated during the cell cycle with the help of other kinases and phosphatases and via proteasomal degradation. Increased levels of Nek2 kinase can promote centrosome amplification (CA), mitotic defects, chromosome instability (CIN), tumor growth, and cancer metastasis. While it remains a highly attractive target for the development of anti-cancer therapeutics, several new roles of the Nek2 enzyme have recently emerged: these include drug resistance, bone, ciliopathies, immune and kidney diseases, and parasitic diseases such as malaria. Therefore, Nek2 is at the interface of multiple cellular processes and can influence numerous cellular signaling networks. Herein, we provide a critical overview of Nek2 kinase biology and discuss the signaling roles it plays in both normal and diseased human physiology. While the majority of research efforts over the last two decades have focused on the roles of Nek2 kinase in tumor development and cancer metastasis, the signaling mechanisms involving the key players associated with several other notable human diseases are highlighted here. We summarize the efforts made so far to develop Nek2 inhibitory small molecules, illustrate their action modalities, and provide our opinion on the future of Nek2-targeted therapeutics. It is anticipated that the functional inhibition of Nek2 kinase will be a key strategy going forward in drug development, with applications across multiple human diseases.<\/jats:p>","DOI":"10.3390\/molecules27020347","type":"journal-article","created":{"date-parts":[[2022,1,7]],"date-time":"2022-01-07T03:46:27Z","timestamp":1641527187000},"page":"347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Nek2 Kinase Signaling in Malaria, Bone, Immune and Kidney Disorders to Metastatic Cancers and Drug Resistance: Progress on Nek2 Inhibitor Development"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-5092","authenticated-orcid":false,"given":"Dibyendu","family":"Dana","sequence":"first","affiliation":[{"name":"Chemistry and Biochemistry Department, Queens College of the City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA"},{"name":"KemPharm Inc., 2200 Kraft Drive, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuhin","family":"Das","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Queens College of the City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Choi","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Queens College of the City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA"},{"name":"Brooklyn Technical High School, 29 Fort Greene Pl, Brooklyn, NY 11217, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashif I.","family":"Bhuiyan","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Queens College of the City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA"},{"name":"Chemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tirtha K.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Cell, Developmental, and Regenerative Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"},{"name":"Mindich Child Health and Development Institute, Department of Pediatrics, Department of Genetics and Genomic Science, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanaji T.","family":"Talele","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John\u2019s University, 8000 Utopia Parkway, Queens, NY 11439, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1799-9730","authenticated-orcid":false,"given":"Sanjai K.","family":"Pathak","sequence":"additional","affiliation":[{"name":"Chemistry and Biochemistry Department, Queens College of the City University of New York, 65-30 Kissena Blvd., Flushing, NY 11367, USA"},{"name":"Chemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA"},{"name":"Biochemistry Doctoral Program, The Graduate Center of the City University of New York, 365 5th Ave, New York, NY 10016, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nrd773","article-title":"Protein kinases\u2014The major drug targets of the twenty-first century?","volume":"1","author":"Cohen","year":"2002","journal-title":"Nat. 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