{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T17:28:16Z","timestamp":1782926896448,"version":"3.54.5"},"reference-count":275,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Membranous nephropathy (MN) is an immune-mediated glomerular disease and the most common cause of nephrotic syndrome in adults. Classical paradigms concentrate on the binding of circulating autoantibodies (e.g., anti-PLA2R, anti-THSD7A) to podocytes, resulting in subepithelial immune deposits, complement activation, and podocyte damage. Nonetheless, mounting evidence suggests that lipid metabolism in podocytes is a crucial regulator of MN pathophysiology. Podocyte slit diaphragms are situated within specialized cholesterol-enriched lipid rafts that orchestrate essential structural and signaling complexes. Disturbances in podocyte lipid metabolism (such as excessive uptake or compromised efflux of cholesterol and fatty acids) lead to \u201clipotoxicity,\u201d marked by mitochondrial oxidative stress, cytoskeletal reorganization, and proinflammatory signaling, ultimately resulting in podocyte hypertrophy, detachment, and apoptosis. This review consolidates recent discoveries regarding the interaction between lipid homeostasis and podocyte biology in minimal change nephropathy (MN). We investigate the interplay between dysregulated lipid profiles, metabolic pathways, and immune injury\u2014specifically, through the promotion of inflammasome activation or the alteration of antigen presentation\u2014and how these interactions may exacerbate glomerular damage. We also talk about translational implications, like how lipid-associated biomarkers (serum lipids, lipidomic signatures, cholesterol-regulatory genes) are related to disease activity and how new therapies (statins, PCSK9 inhibitors, cyclodextrins, nuclear receptor agonists, etc.) might be used to target the metabolic part of MN. The \u201clipid\u2013podocyte axis\u201d connects podocyte lipid metabolism with immune pathogenesis. This gives us a new way to think about MN and opens up new possibilities for diagnosis and treatment.<\/jats:p>","DOI":"10.3389\/fmed.2026.1722758","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T12:52:31Z","timestamp":1772628751000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The lipid\u2013podocyte axis: emerging clues in membranous nephropathy pathogenesis"],"prefix":"10.3389","volume":"13","author":[{"given":"Sichao","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Office of Research, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shoulin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong\u2019an","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfan","family":"Liu","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"sfae243","DOI":"10.1093\/ckj\/sfae243","article-title":"Therapeutic targets in membranous nephropathy: plasma cells and complement","volume":"17","author":"Tomas","year":"2024","journal-title":"Clin Kidney J"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1009864","DOI":"10.3389\/fimmu.2022.1009864","article-title":"The role of the complement system in primary membranous nephropathy: a narrative review in the era of new therapeutic targets","volume":"13","author":"So","year":"2022","journal-title":"Front Immunol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1159\/000518132","article-title":"The updates of podocyte lipid metabolism in proteinuric kidney disease","volume":"7","author":"Sun","year":"2021","journal-title":"Kidney Dis"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"12505","DOI":"10.2147\/JIR.S530737","article-title":"The lipid-oxidative stress axis: novel therapeutic targets for podocytopathy","volume":"18","author":"Liu","year":"2025","journal-title":"J Inflamm Res"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"994","DOI":"10.1016\/j.kint.2025.01.040","article-title":"A new era in nephrology: the role of super-resolution microscopy in research, medical diagnostic, and drug discvery","volume":"107","author":"Siegerist","year":"2025","journal-title":"Kidney Int"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1159\/000528713","article-title":"Super-resolution microscopy: a technique to revolutionize research and diagnosis of glomerulopathies","volume":"3","author":"Siegerist","year":"2022","journal-title":"Glomerular Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/978-1-0716-3179-9_14","article-title":"Quantitative imaging of podocyte foot processes in the kidney using confocal and STED microscopy","volume-title":"Kidney research. 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