Chloride channel protein 5 (ClC-5)

Chloride channel protein 5 (ClC-5, encoded by the CLCN5 gene) is a voltage-dependent chloride/proton exchanger predominantly expressed in the kidneys, especially within proximal tubular cells. Functionally, ClC-5 mediates the exchange of chloride ions and protons across the membrane of endosomal compartments, enabling proper acidification necessary for receptor-mediated endocytosis and the uptake of low-molecular-weight proteins and albumin. Dysfunction due to CLCN5 mutations causes Dent disease 1, an X-linked renal disorder characterized by proteinuria, renal tubular defects, nephrolithiasis, and progressive kidney failure. The protein belongs to the ClC family of ion channels, forming dimers with a unique structure enabling selective transport functions. As of now, there are no approved drugs that directly target ClC-5; patient management focuses on addressing symptoms and complications of the underlying renal disease.

Other names

Chloride voltage-gated channel 5H(+)/Cl(-) exchange transporter 5CLCN5ClC-5CLCK2DENT1DENTSXLRHhClC-K2hCIC-K2CLC5XRNChloride channel protein 5Chloride transporter ClC-5NPHL1NPHL2chloride channel, voltage-sensitive 5voltage-gated chloride ion channel CLCN5

Not applicable (no approved drugs directly targeting ClC-5); theoretical interventions could involve modulation of endosomal acidification or chloride ion transport.