A role for chloride transport in lysosomal protein degradation.

Loss of the lysosomal chloride transport protein ClC-7 leads to complex phenotypes in mice and man, including osteopetrosis, accumulation of lysosomal storage material, and neurodegeneration. Using novel tissue-specific ClC-7 knockout mice, we have shown that upon loss of ClC-7, lysosomal degradation of endocytosed protein is slowed down and accumulation of autophagosomes occurs.