{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:09:53Z","timestamp":1792004993696,"version":"4.4.0"},"reference-count":124,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Growing evidence suggests that persistent oral infectious diseases (OIDs) contribute to systemic disease, highlighting the importance of understanding their pathogenic mechanisms. Conventional dental treatments, primarily mechanical debridement, surgical intervention, or antimicrobial therapy, often struggle to fully control inflammation or prevent progressive tissue destruction. The nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) inflammasome is a key regulator of innate immunity, mediating the maturation of proinflammatory cytokines (IL-1\u03b2 and IL-18) and the pyroptosis-inducing protein gasdermin D. Dysregulated or excessive activation of NLRP3 contributes to the initiation and progression of major oral diseases, including periodontitis, peri-implantitis, pulpitis, and oral mucosal inflammation. Despite growing interest in NLRP3, comprehensive and up-to-date reviews integrating its pathogenic mechanisms and therapeutic potential remain limited. This review summarizes current and past evidence on the role of the NLRP3 inflammasome in oral disease development, highlights emerging pharmacological strategies, and outlines future research directions. Existing studies demonstrate that microbial components and danger signals from injured tissues activate NLRP3, thereby amplifying inflammation, tissue degradation, and bone resorption. Preclinical studies indicate that inflammasome inhibitors and several natural compounds reduce tissue damage; however, their clinical translation remains limited. These findings emphasize the need for deeper understanding of NLRP3-mediated pathways, with translational and clinical research offering promising therapeutic opportunities for oral diseases.<\/jats:p>","DOI":"10.3390\/ijms27021098","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:16:59Z","timestamp":1769159819000},"page":"1098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Emerging Role of the NLRP3 Inflammasome in the Onset of Oral Diseases and Its Potential as a Therapeutic Target"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-238X","authenticated-orcid":false,"given":"Mohammad Ibtehaz","family":"Alam","sequence":"first","affiliation":[{"name":"Department of Periodontology & Oral Pathology, University Dental College, Dhaka 1217, Bangladesh"},{"name":"Department of Endodontics, Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health, Farmington, CT 06030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7398-8255","authenticated-orcid":false,"given":"Fatima","family":"Farhana","sequence":"additional","affiliation":[{"name":"Department of Prosthodontics, University Dental College, Dhaka 1217, Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiko","family":"Sakai","sequence":"additional","affiliation":[{"name":"Department of Medical Research and Development for Oral Disease, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852-8588, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,22]]},"reference":[{"key":"ref_1","unstructured":"GBD 2021 Oral Disorders Collaborators (2025). 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