Chloride accumulation in endosomes and lysosomes: facts checked in mice

Loss of the ClC-3 chloride/proton exchanger found in intracellular compartments leads to marked neurodegeneration. New genetic work by Weinert et al (2020) now shows that selective impairment of ClC-3's ion exchange activity is sufficient to elicit this severe phenotype in vivo. ClC-3 cooperates with the closely related ClC-4 in protecting endolysosomal chloride balance and neuronal integrity.