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Immunol."],"abstract":"<jats:p>Diabetic kidney disease (DKD) is the main cause of end-stage renal disease (ESRD) worldwide. Podocytes are important components of the glomerular filtration barrier, which is located between glomerular capillary endothelial cells and the basement membrane, and is essential for maintaining normal renal function. Its injury is a key factor in the progression of DKD. Lipid homeostasis plays an important role in maintaining the normal physiological function of cells. In recent years, many studies have revealed that lipid metabolism disorders play a core role in driving podocyte injury, but its specific mechanism network has not been systematically characterized. This article systematically reviews the latest evidence from recent years, indicating that lipid metabolism disorders mainly lead to podocyte structure and dysfunction, apoptosis and extracellular matrix deposition through key pathways such as lipid peroxidation, abnormal sphingolipid metabolism and abnormal cholesterol accumulation. In addition, the review summarizes the core regulatory roles of related signaling pathways such as Sterol Regulatory Element-Binding Protein 1 (SREBP1), Peroxisome Proliferator-Activated Receptor \u03b1 (PPAR\u03b1) and NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in this process. This review emphasizes that lipid metabolism disorder is a key driver of podocyte injury in DKD. This provides a theoretical basis for a new therapy for DKD that focuses on lipid metabolism as the core strategy. Future research should focus on elucidating the interaction network between these pathways and promoting the clinical transformation of related intervention strategies to delay disease progression.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1764023","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T04:21:00Z","timestamp":1783311660000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Lipid metabolism drives podocyte injury in diabetic kidney disease"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiazhen","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhitao","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Shandong Provincial 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