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Recent research identifies the ectodysplasin A2 receptor (EDA2R) as a key regulator of inflammaging and a novel biomarker of ageing, with its expression increasing with age across diverse tissues in humans and animal models. Elevated\n                    <jats:italic>EDA2R<\/jats:italic>\n                    gene expression is associated with accelerated ageing, cellular senescence, frailty, obesity, acne, radiation response and increased levels of inflammatory, renal, cardiac and vascular biomarkers. Similarly, elevated EDA2R protein levels, a critical component of the proteomic ageing clock, are associated with a wide range of conditions, including cardiovascular diseases, dementia, Parkinson's disease, mood disorders, post\u2010traumatic stress disorder, various cancers, osteoarthritis, digestive diseases, diabetes, obesity, chronic obstructive pulmonary disease, ear and eye diseases, renal impairment, systemic autoimmune diseases, anaemia, bacterial infections, myositis, frailty, accelerated biological ageing, shorter telomere length, decreased healthspan and longevity, higher all\u2010cause mortality and overall poor health. Beyond serving as a biomarker, EDA2R actively drives ageing, as its overexpression induces inflammation and tissue damage, whereas its inhibition mitigates these effects. Mechanistically, EDA2R activates non\u2010canonical and canonical NF\u2010\u03baB signalling, promoting pro\u2010inflammatory and catabolic processes that accelerate ageing phenotypes. Genetic variants of\n                    <jats:italic>EDA2R<\/jats:italic>\n                    are linked to alopecia, facial ageing, lipid profiles and prostate cancer. This review explores the structure and function of the\n                    <jats:italic>EDA2R<\/jats:italic>\n                    gene and protein, its role in tissue\u2010specific ageing, and its therapeutic potential for multiple diseases. Although specific EDA2R antagonists are not yet available, interventions like calorie restriction, physical activity and specific supplements show promise in lowering EDA2R levels.\n                  <\/jats:p>","DOI":"10.1111\/acel.70282","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T09:39:21Z","timestamp":1762249161000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Roles of\n                    <scp>EDA2R<\/scp>\n                    in Ageing and Disease"],"prefix":"10.1111","volume":"24","author":[{"given":"Gemma","family":"Farrington","sequence":"first","affiliation":[{"name":"School of Biological and Environmental Sciences Liverpool John Moores University  Liverpool UK"},{"name":"Institute for Health Research Liverpool John Moores University  Liverpool 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