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These disorders are characterized by cystogenesis, driven by dysregulated ciliary signaling, leading to uncontrolled epithelial proliferation, aberrant growth, and loss of cellular polarity. The clinical trajectory evolves from initial cyst formation to advanced tubulointerstitial fibrosis and progressive renal failure. This progression is governed by pathogenic variants in genes encoding ciliary proteins. While advancements in genetic testing have established prenatal diagnosis as a pivotal tool for early identification, definitive diagnosis and therapeutic intervention remain challenging. These difficulties stem from several factors: incomplete understanding of the molecular mechanisms underlying cyst formation and fibrosis; limitations in prenatal diagnostic accuracy owing to phenotypic overlap and incomplete penetrance; and the marked genetic heterogeneity and diverse clinical trajectories of renal ciliopathies. Existing studies have primarily focused on unidirectional modulation of individual pathways, whereas the systematic integration of signaling network cascades remains largely unaddressed. This review systematically elucidates the molecular mechanisms and aberrant signaling pathways in renal ciliopathies, links genetic heterogeneity to clinical phenotypes, and lays a theoretical basis for prenatal diagnosis and novel therapies.<\/jats:p>","DOI":"10.1002\/ccs3.70102","type":"journal-article","created":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T12:38:06Z","timestamp":1786538286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Broadening horizons: Pathogenesis and therapeutics of renal ciliopathies"],"prefix":"10.1002","volume":"20","author":[{"given":"Qiaowei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou University  Zhengzhou 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