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However, the key molecules involved in fibrogenesis remain unclear. Glucuronyl C5\u2010epimerase (\n                    <jats:italic>Hsepi<\/jats:italic>\n                    , gene name,\n                    <jats:italic>Glce<\/jats:italic>\n                    ) is a key enzyme that catalyzes the biosynthesis of heparan sulfate (HS) chains attached to HS proteoglycans that are ubiquitously located on the cell membrane. Homozygous\n                    <jats:italic>Glce<\/jats:italic>\n                    \u2010\/\u2010 mice may exhibit embryonic lethality and multi\u2010organ defects. However, the role of\n                    <jats:italic>Glce<\/jats:italic>\n                    in kidney fibrosis remains unclear. This study investigated the contribution of\n                    <jats:italic>Glce<\/jats:italic>\n                    to kidney development and its role in renal fibrosis pathogenesis. Here, it shows that\n                    <jats:italic>Glce<\/jats:italic>\n                    expression is significantly attenuated in the kidneys of patients with renal fibrosis and in animal models. Renal tubular\u2010specific\n                    <jats:italic>Glce<\/jats:italic>\n                    deletion in mice exacerbated kidney fibrosis, while AAV\u2010mediated\n                    <jats:italic>Glce<\/jats:italic>\n                    overexpression in unilateral ureteral obstruction\u2010treated mice ameliorated kidney fibrosis via the TGF\u2010\u03b2\/Smad2\/3 signaling pathway. Mechanistic studies indicate that\n                    <jats:italic>Glce<\/jats:italic>\n                    protein may bind to epidermal growth factor receptor (EGFR) to inactivate EGFR\/ERK signaling and further impede TGF\u2010\u03b2\/Smad signaling pathway and renal fibrosis in\n                    <jats:italic>Glce<\/jats:italic>\n                    \u2010\/\u2010 and wild\u2010type mice. Notably, the anti\u2010fibrotic function is independent of\n                    <jats:italic>Glce<\/jats:italic>\n                    enzymatic activation. These findings reveal a novel function of\n                    <jats:italic>Glce<\/jats:italic>\n                    , which plays a key role in kidney fibrosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202416216","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T13:03:29Z","timestamp":1754917409000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["D\u2010glucuronyl C5\u2010Epimerase Binds to EGFR to Suppress Kidney Fibrosis"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiaoqi","family":"Jing","sequence":"first","affiliation":[{"name":"Carbohydrate\u2010Based Drug Research Center CAS Key Laboratory of Receptor Research State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Chinese Academy of Sciences  Shanghai 201203 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