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This review synthesizes current research on 5\u2010HT metabolism (biosynthesis, transport, and degradation), 5\u2010HT receptor\u2010mediated signaling pathways (seven receptor families and 14 subtypes), and broad biological functions of 5\u2010HT. We emphasize the roles of 5\u2010HT in both health and disease, with a particular focus on its emerging significance in the tumor immune microenvironment. Studies have shown that dysregulated 5\u2010HT signaling is associated with various pathological conditions, including functional gastrointestinal disorders, psychiatric diseases, metabolic disorders, and cancer progression. Notably, this review describes novel mechanisms by which 5\u2010HT modulates tumor immunity, including its effects on macrophage polarization, dendritic cell function, T cell activity, and PD\u2010L1 expression, and it explores the therapeutic potential of targeting 5\u2010HT\u2010associated pathways. Promising therapeutic strategies that target 5\u2010HT include combining selective serotonin reuptake inhibitors with immune checkpoint inhibitors, inhibiting key metabolic enzymes (e.g., Tph1 and MAO\u2010A), and developing receptor subtype\u2010specific agents (e.g., 5\u2010HT\n                    <jats:sub>7<\/jats:sub>\n                    R antagonists). These findings position the 5\u2010HT system as a pivotal target for next\u2010generation precision therapeutics across multiple disease domains.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70383","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T06:52:05Z","timestamp":1757487125000},"source":"Crossref","is-referenced-by-count":46,"title":["Serotonin (5\u2010Hydroxytryptamine): Metabolism, Signaling, Biological Functions, Diseases, and Emerging Therapeutic Opportunities"],"prefix":"10.1002","volume":"6","author":[{"given":"Yuxin","family":"Zhang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Department of General Surgery Nanjing Drum Tower Hospital The Affiliated Hospital of Medical School Medical School Nanjing University  Nanjing China"},{"name":"Jinan Microecological Biomedicine Shandong Laboratory Building 1, Jinan Medical and Health Science and Technology Innovation Industrial Park  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 Fuzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Wu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Pharmaceutical Biotechnology Department of General Surgery Nanjing Drum Tower Hospital The Affiliated Hospital of Medical School Medical School Nanjing University  Nanjing China"},{"name":"Jinan Microecological Biomedicine Shandong Laboratory Building 1, Jinan Medical and Health Science and Technology Innovation Industrial Park  Jinan City Shandong China"},{"name":"\u201cNanjing University\u2010Gulou\u201d Joint Laboratory of AI and Healthcare Bigdata National Institute of Healthcare Data Science at Nanjing University School of Life Sciences Jiangsu Key Laboratory of Molecular Medicine Nanjing University  Nanjing 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