Pathogenic variants in the CLCN5 gene encoding the chloride-hydrogen exchanger ClC-5 cause Dent’s disease type 1, a genetic disorder of the endolysosomal pathway in the proximal tubules of the kidneys. A hallmark of this disease is the downregulation of the protein uptake receptor consisting of megalin, cubilin and amnionless, causing low-molecular-weight proteinuria. Why these receptors are downregulated is not fully understood.
Kidney International published a clinical update in Research Highlights on 11 Feb 2026.
The item focuses on A Drosophila model for Dent’s disease type 1 revealed impaired endoplasmic reticulum export of Cubilin as pathogenic mechanism.
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