Neuronal Ceroid Lipofuscinosis 6 (NCL6) is a neurodegenerative, lysosomal storage disease. It is caused by a deficiency of the transmembrane protein ceroid-lipofuscinosis neuronal protein 6 (CLN6) that resides in the endoplasmic reticulum. In this project the lysosomal proteome changes in NCL6 were investigated. Therefore, lysosomes were purifiedfrom liver tissue of CLN6 knock-out mice, the proteins were labeled by TMT and the CLN6 proteome was compared to wild type controls. Lysosome purification was obtained by either isolation of tritosomes or differential centrifugation generating 20,000 g pellets.