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Through their foot processes and slit diaphragm structures, podocytes confer selective permeability to the glomerular filtration barrier and play a critical role in maintaining kidney function. Podocyte damage is characterized by foot process effacement, loss of slit diaphragm proteins, reorganization of the actin cytoskeleton, and apoptosis, and plays a central role in the pathogenesis of proteinuric glomerular diseases such as minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, and diabetic nephropathy. This narrative review examines podocyte biology, the main molecular pathways of podocyte damage (RhoA\/ROCK, TGF-\u03b2, mTOR, and oxidative stress), the clinical presentations of podocytopathies, and treatment strategies ranging from RAAS blockade, SGLT2 inhibitors, cytoskeletal stabilizers, gene therapy, to regenerative medicine approaches. By highlighting recent findings and translational challenges, the importance of podocyte-focused therapies in glomerular diseases is emphasized. Future studies aim to preserve podocyte integrity and prevent progressive kidney disease through personalized molecular therapies and multidisciplinary research.<\/jats:p>","DOI":"10.1177\/00368504261475956","type":"journal-article","created":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T23:00:20Z","timestamp":1786402820000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Podocyte dysfunction in kidney diseases: Mechanisms and therapeutic advances"],"prefix":"10.1177","volume":"109","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2913-6866","authenticated-orcid":false,"given":"Shams","family":"Ismayilova","sequence":"first","affiliation":[{"name":"Ege University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onur","family":"Mutlu","sequence":"additional","affiliation":[{"name":"Karadeniz Technical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamila","family":"Bayramova","sequence":"additional","affiliation":[{"name":"Azerbaijan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afig","family":"Berdeli","sequence":"additional","affiliation":[{"name":"Ege University"},{"name":"Ege University"},{"name":"Ege University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,8,10]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1564847"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2024.01.042"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2025.08.028"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115670"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1578045"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1186\/s41073-019-0064-8"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfaf332"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells9071700"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2026.04.016"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202502934R"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-017-0069"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1159\/000528713"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.771931"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10157-024-02465-y"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26189159"},{"issue":"2","key":"e_1_3_6_17_2","first-page":"102","article-title":"NPHS2 gene sequencing results in children of the Azerbaijani population with different types of nephrotic syndrome caused by chronic glomerulonephritis","volume":"120","author":"Baylarov R","year":"2019","unstructured":"Baylarov R, Baylarova R, Berdeli A, et al. NPHS2 gene sequencing results in children of the Azerbaijani population with different types of nephrotic syndrome caused by chronic glomerulonephritis. Bratisl Lek Listy 2019; 120(2): 102\u2013105. https:\/\/doi.org\/10.4149\/BLL_2019_016","journal-title":"Bratisl Lek Listy"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000964"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49854-1"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-024-06127-3"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines14030621"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26199316"},{"issue":"4","key":"e_1_3_6_23_2","first-page":"1100","article-title":"Mechanistic Insights Into Redox Damage of the Podocyte in Proteinuric Kidney Disease","volume":"78","author":"Ilatovskaya DV","year":"2025","unstructured":"Ilatovskaya DV, Levchenko V, Winsor K, et al. 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