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The oral cavity is continuously exposed to food-derived compounds, microbial metabolites, volatile organic compounds, and inflammation-associated metabolites, yet the molecular roles of oral ORs remain incompletely defined. This review critically synthesizes current evidence for OR expression and signaling in oral tissues and associated cell populations, with emphasis on ligand\u2013receptor\u2013signaling relationships and disease relevance. Functional OR signaling has been demonstrated in mammalian taste cells, while emerging transcriptomic studies in oral mucosa and transcriptomic\/localization studies in the periodontal ligament indicate OR-related programs during tissue-specific or repair-associated states. Candidate metabolic axes, including short-chain fatty acids and lactate linked to OR51E1\/OR51E2\/Olfr78-related pathways in non-oral models, provide testable mechanistic hypotheses for microbiome\u2013host communication in periodontitis and oral cancer; however, direct causal validation in oral disease models remains limited. We propose an evidence-tiered framework integrating spatial expression mapping, metabolomics-guided deorphanization, receptor perturbation, and longitudinal oral-fluid profiling. Oral ORs should currently be regarded as candidate molecular modulators and components of multimodal biomarker strategies rather than validated standalone diagnostic or therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms27136093","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T17:27:31Z","timestamp":1783531651000},"page":"6093","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ectopic Olfactory Receptors in Oral Health and Disease: Molecular Links Between Chemosensing, Tissue Repair, Inflammation, and Cancer"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3197-3069","authenticated-orcid":false,"given":"Jun","family":"Ohshima","sequence":"first","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutake","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shotaro","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Preventive Dentistry, Graduate School of Dentistry, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikako","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Restorative Dentistry and Endodontology, Graduate School of Dentistry, The University of Osaka, Suita 565-0871, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/bs.mcb.2015.11.003","article-title":"Olfactory Receptor Signaling","volume":"132","author":"Antunes","year":"2016","journal-title":"Methods Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1073\/pnas.0307882100","article-title":"The Human Olfactory Receptor Gene Family","volume":"101","author":"Malnic","year":"2004","journal-title":"Proc. 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