Renal-Electrolyte Division, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Function (Oxf). 2020;1(2):zqaa017. doi: 10.1093/function/zqaa017. Epub 2020 Sep 11.
Dent disease (DD) is a rare kidney disorder caused by mutations in the Cl/H exchanger ClC-5. Extensive physiologic characterization of the transporter has begun to illuminate its role in endosomal ion homeostasis. Nevertheless, we have yet to understand how loss of ClC-5 function in the kidney proximal tubule impairs membrane traffic of megalin and cubilin receptors to cause the low molecular weight proteinuria characteristic of DD. This review identifies open questions that remain to be answered, evaluates the current literature addressing these questions, and suggests new testable models that may link loss of ClC-5 function to tubular proteinuria in DD.
Dent 病（DD）是一种罕见的肾脏疾病，由 Cl/H 交换器 ClC-5 的突变引起。对该转运蛋白的广泛生理特性研究已经开始阐明其在内体离子稳态中的作用。然而，我们仍不了解肾脏近端小管中 ClC-5 功能的丧失如何影响 megalin 和 cubilin 受体的膜运输，从而导致 DD 特征性的低分子量蛋白尿。本综述确定了仍待回答的开放性问题，评估了目前针对这些问题的文献，并提出了新的可检验模型，这些模型可能将 ClC-5 功能丧失与 DD 的管状蛋白尿联系起来。
