{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T01:36:58Z","timestamp":1785461818392,"version":"3.56.0"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Dysregulation of the innate immune system is a key feature of autoinflammatory disorders, characterized by recurrent or chronic inflammation in the absence of high-titer autoantibodies and antigen-specific T cells. Among regulators of innate immunity, NLRP12 has emerged as an important modulator of inflammatory signaling pathways. As a member of the nucleotide-binding oligomerization domain-like receptor (NLR) family, NLRP12 negatively regulates nuclear factor (NF)-\u03baB activity and contributes to immune homeostasis. However, the clinical significance of NLRP12 variants and their association with disease phenotypes remain incompletely understood. This study aims to summarize current knowledge on the molecular role of NLRP12 and its involvement in autoinflammatory manifestations. Methods: A narrative review of the literature on NLRP12\u2019s molecular functions and role in autoinflammatory diseases was performed. In addition, a cohort of 20 patients with recurrent fevers carrying NLRP12 variants was analyzed from a clinical perspective, evaluating genetic findings and clinical features. Results: Available evidence indicates that NLRP12 regulates inflammatory signaling, particularly through modulation of NF-\u03baB activity. Variants in the NLRP12 gene have been associated with a spectrum of autoinflammatory phenotypes, ranging from periodic fever syndromes to broader systemic inflammatory manifestations. Clinical evaluation of the cohort confirmed the heterogeneity of disease presentations among individuals carrying NLRP12 variants. Conclusions: NLRP12 plays an important role in the regulation of innate immune responses and may contribute to autoinflammatory phenotypes. Integrating molecular data with clinical observations may improve the understanding of NLRP12 variants and support more accurate diagnostic and therapeutic strategies.<\/jats:p>","DOI":"10.3390\/genes17040421","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T07:57:55Z","timestamp":1775116675000},"page":"421","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["NLRP12 as a Regulator of Inflammation: Insights into the Correlation with Autoinflammatory Disorders"],"prefix":"10.3390","volume":"17","author":[{"given":"Beatrice","family":"Rosa","sequence":"first","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4707-2242","authenticated-orcid":false,"given":"Elisabetta","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Sezione di Medicina Genomica, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Pietrobono","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Public Health, Sezione di Medicina Genomica, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9079-9175","authenticated-orcid":false,"given":"Eugenio","family":"Sangiorgi","sequence":"additional","affiliation":[{"name":"UOSD Laboratorio di Genetica Medica, Ospedale Santa Rosa (Belcolle), 01100 Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6775-5972","authenticated-orcid":false,"given":"Fiorella","family":"Gurrieri","sequence":"additional","affiliation":[{"name":"Research Unit of Medical Genetics, Department of Medicine, University Campus-Biomedico of Rome, 00128 Rome, Italy"},{"name":"Operative Research Unit of Medical Genetics, Fondazione Policlinico Universitario Campus Bio-Medico, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5104-1521","authenticated-orcid":false,"given":"Pietro","family":"Chiurazzi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Sezione di Medicina Genomica, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-0382","authenticated-orcid":false,"given":"Ludovico Luca","family":"Sicignano","sequence":"additional","affiliation":[{"name":"Department of Aging, Orthopaedical and Rheumatological Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Periodic Fevers Research Center, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2131-2110","authenticated-orcid":false,"given":"Elena","family":"Verrecchia","sequence":"additional","affiliation":[{"name":"Department of Aging, Orthopaedical and Rheumatological Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Periodic Fevers Research Center, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7410-8351","authenticated-orcid":false,"given":"Maurizio","family":"Genuardi","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Sezione di Medicina Genomica, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"},{"name":"Periodic Fevers Research Center, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7032-7779","authenticated-orcid":false,"given":"Donato","family":"Rigante","sequence":"additional","affiliation":[{"name":"Periodic Fevers Research Center, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"},{"name":"Department of Life Sciences and Public Health, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1560-3907","authenticated-orcid":false,"given":"Raffaele","family":"Manna","sequence":"additional","affiliation":[{"name":"Periodic Fevers Research Center, Universit\u00e0 Cattolica Sacro Cuore, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3129","DOI":"10.1093\/rheumatology\/keaa304","article-title":"NLRP12 gene mutations and auto-inflammatory diseases: Ever-changing evidence","volume":"59","author":"Cifani","year":"2020","journal-title":"Rheumatology"},{"key":"ref_2","first-page":"RA179","article-title":"Autoinflammatory syndromes behind the scenes of recurrent fevers in children","volume":"15","author":"Rigante","year":"2009","journal-title":"Med. 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