Chloride transport protein 6 (CLCN6)

Chloride transport protein 6 (CLCN6, ClC-6) is an intracellular, predominantly neuronal, voltage-gated chloride/proton exchanger localized to late endosomes and lysosomes, where it mediates Cl^–/H^+ exchange essential for normal endolysosomal acidification and neuronal function[2][4]. Structurally, it is a dimeric protein with each monomer consisting of an 18-helix transmembrane domain and cytoplasmic cystathionine β-synthase (CBS) domains, and it exhibits complex voltage-dependent gating properties distinct from plasma-membrane CLC channels[2][3]. Loss-of-function or gain-of-function mutations in CLCN6 are established genetic causes of severe early-onset neurodegenerative disease, highlighting its essential role in the nervous system[2][3][4]. There are currently no known drugs that target ClC-6 directly in clinical use.

Other names

ClC-6CLC-6H(+)/Cl(-) exchange transporter 6KIAA0046Chloride channel protein 6Chloride voltage-gated channel 6CONRIBA

Not established for therapeutic drugs; native action is voltage-gated, pH-sensitive Cl^–/H^+ exchange (antiport) in endosomal compartments[2][4].