{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:58:25Z","timestamp":1790773105278,"version":"4.1.0"},"reference-count":201,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nephrotic Syndrome Trust and UKRI Medical Research Council","award":["MR\/R013942\/1"],"award-info":[{"award-number":["MR\/R013942\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Podocytopathies encompass a spectrum of glomerular disorders driven by structural and functional impairments in podocytes: specialized cells critical for maintaining the glomerular filtration barrier. Dysregulation of key podocyte components\u2014such as slit-diaphragm proteins (nephrin, podocin), cytoskeletal regulators (ACTN4, TRPC6), and adhesion complexes (integrins, dystroglycan)\u2014leads to proteinuria and progressive glomerulosclerosis. Current therapies often fail to address underlying genetic or molecular defects, particularly in hereditary or refractory cases. Gene therapy has emerged as a transformative approach, leveraging adeno-associated viral (AAV) vectors, CRISPR-based editing, and RNA modulation to correct pathogenic mutations or restore disrupted pathways. Recent advances in capsid engineering, tissue-specific promoters, and delivery strategies have enhanced podocyte targeting while minimizing off-target effects. Preclinical successes, including AAV-mediated rescue of NPHS2-associated nephrotic syndrome and complement modulation in IgA nephropathy, highlight the therapeutic potential. However, challenges such as immune responses, vector biodistribution, and disease heterogeneity remain. This review synthesizes the molecular mechanisms underlying podocytopathies, evaluates current gene-therapy strategies, and discusses translational hurdles and future directions, including patient-derived organoid models and combinatorial therapies. By bridging mechanistic insights with innovative gene-based interventions, this work underscores the promise of precision medicine in revolutionizing the treatment of podocytopathies.<\/jats:p>","DOI":"10.1093\/ckj\/sfaf332","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:03:58Z","timestamp":1762002238000},"source":"Crossref","is-referenced-by-count":4,"title":["Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy"],"prefix":"10.1093","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2831-1906","authenticated-orcid":false,"given":"Nadia","family":"Tavakolidakhrabadi","sequence":"first","affiliation":[{"name":"Bristol Medical School, Bristol Renal, University of Bristol , Dorothy Hodgkin Building, Whitson Street, Bristol ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9537-9783","authenticated-orcid":false,"given":"Wen Y","family":"Ding","sequence":"additional","affiliation":[{"name":"Bristol Medical School, Bristol Renal, University of Bristol , Dorothy Hodgkin Building, Whitson Street, Bristol ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin I","family":"Welsh","sequence":"additional","affiliation":[{"name":"Bristol Medical School, Bristol Renal, University of Bristol , Dorothy Hodgkin Building, Whitson Street, Bristol ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moin A","family":"Saleem","sequence":"additional","affiliation":[{"name":"Bristol Medical School, Bristol Renal, University of Bristol , Dorothy Hodgkin Building, Whitson Street, Bristol ,","place":["UK"]},{"name":"Bristol Royal Hospital for Children Bristol Royal Hospital for Children, Department of 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