{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:02:23Z","timestamp":1792587743582,"version":"4.5.0"},"reference-count":145,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T00:00:00Z","timestamp":1599523200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Fibulin-3 (also known as EGF-containing fibulin extracellular matrix protein 1 (EFEMP1)) is a secreted extracellular matrix glycoprotein, encoded by the EFEMP1 gene that belongs to the eight-membered fibulin protein family. It has emerged as a functionally unique member of this family, with a diverse array of pathophysiological associations predominantly centered on its role as a modulator of extracellular matrix (ECM) biology. Fibulin-3 is widely expressed in the human body, especially in elastic-fibre-rich tissues and ocular structures, and interacts with enzymatic ECM regulators, including tissue inhibitor of metalloproteinase-3 (TIMP-3). A point mutation in EFEMP1 causes an inherited early-onset form of macular degeneration called Malattia Leventinese\/Doyne honeycomb retinal dystrophy (ML\/DHRD). EFEMP1 genetic variants have also been associated in genome-wide association studies with numerous complex inherited phenotypes, both physiological (namely, developmental anthropometric traits) and pathological (many of which involve abnormalities of connective tissue function). Furthermore, EFEMP1 expression changes are implicated in the progression of numerous types of cancer, an area in which fibulin-3 has putative significance as a therapeutic target. Here we discuss the potential mechanistic roles of fibulin-3 in these pathologies and highlight how it may contribute to the development, structural integrity, and emergent functionality of the ECM and connective tissues across a range of anatomical locations. Its myriad of aetiological roles positions fibulin-3 as a molecule of interest across numerous research fields and may inform our future understanding and therapeutic approach to many human diseases in clinical settings.<\/jats:p>","DOI":"10.3390\/biom10091294","type":"journal-article","created":{"date-parts":[[2020,9,8]],"date-time":"2020-09-08T09:03:48Z","timestamp":1599555828000},"page":"1294","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":74,"title":["The Pathophysiological Significance of Fibulin-3"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-5812","authenticated-orcid":false,"given":"Imogen","family":"Livingstone","sequence":"first","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4037-5857","authenticated-orcid":false,"given":"Vladimir N.","family":"Uversky","sequence":"additional","affiliation":[{"name":"Laboratory of New Methods in Biology, Institute for Biological Instrumentation, Russian Academy of Sciences, Federal Research Center \u201cPushchino Scientific Center for Biological Research of the Russian Academy of Sciences\u201d, Pushchino 142290, Moscow Region, Russia"},{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic","family":"Furniss","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK"},{"name":"Department of Plastic and Reconstructive Surgery, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4944-123X","authenticated-orcid":false,"given":"Akira","family":"Wiberg","sequence":"additional","affiliation":[{"name":"Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK"},{"name":"Department of Plastic and Reconstructive Surgery, Oxford University Hospitals NHS Foundation Trust, John Radcliffe Hospital, Oxford OX3 9DU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1128\/MCB.15.1.120","article-title":"An overexpressed gene transcript in senescent and quiescent human fibroblasts encoding a novel protein in the epidermal growth factor-like repeat family stimulates DNA synthesis","volume":"15","author":"Lumpkin","year":"1995","journal-title":"Mol. 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