{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:00:51Z","timestamp":1789945251706,"version":"4.0.1"},"reference-count":132,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T00:00:00Z","timestamp":1789948800000},"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. Genet."],"abstract":"<jats:p>Podocyte injury is widely recognized as a central driver of glomerular proteinuria and progression to chronic kidney disease. Although proteinuria can originate from multiple components of the glomerular filtration barrier, genetic and experimental studies increasingly implicate podocyte dysfunction as a dominant and convergent mechanism in many disease contexts. In recent years, the application of next-generation sequencing has broadened the spectrum of genes linked to proteinuric kidney disorders. These genes are no longer confined to structural elements of the slit diaphragm or cytoskeleton but also involve pathways governing vesicular trafficking, nuclear regulation, mitochondrial function, and interactions with the extracellular matrix. Despite their functional diversity, alterations in these pathways often produce overlapping clinical phenotypes, suggesting convergence at the level of cellular homeostasis rather than at a single molecular endpoint. Experimental observations further indicate that podocytes maintain their structural and functional integrity through coordinated regulation across multiple cellular compartments. Mechanical cues originating from the glomerular basement membrane are interpreted through cytoskeletal signaling; membrane trafficking processes determine the localization and turnover of key slit diaphragm proteins; nuclear mechanisms shape transcriptional responses; mitochondrial systems contribute to metabolic adaptation under stress conditions. Perturbations in any of these processes may not remain localized but can extend across interconnected pathways, gradually impairing filtration barrier function. Current evidence therefore favors a multi-layer network perspective in which glomerular proteinuria reflects a breakdown of coordinated podocyte homeostasis across interconnected cellular compartments.<\/jats:p>","DOI":"10.3389\/fgene.2026.1934937","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:10:23Z","timestamp":1789942223000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Emerging genetic mechanisms of glomerular proteinuria: a podocyte-centered multi-layer network perspective"],"prefix":"10.3389","volume":"17","author":[{"given":"Meijia","family":"Fu","sequence":"first","affiliation":[{"name":"Shandong First Medical University (Shandong Academy of Medical Sciences)","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayi","family":"Lin","sequence":"additional","affiliation":[{"name":"Shandong First Medical University (Shandong Academy of Medical Sciences)","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Shandong Provincial Hospital Affiliated to Shandong First Medical University","place":["Jinan, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1038\/s41588-024-01802-x","article-title":"Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression","volume":"56","author":"Abedini","year":"2024","journal-title":"Nat. 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