Studies have shown that the majority of Parkinson's disease patients have at least one putative damaging variant in a lysosomal storage disorder gene (60%) and in about 10% of sporadic PD subjects, the disease is associated with mutations in GBA1, a gene coding for glucocerebrosidase, a lysosomal hydrolase. However, the precise cellular and lysosome-specific alterations upon loss of glucocerebrosidase are not established. The aim of this study is to characterize the proteome-wide changes at the cellular and lysosomal level in H4 cells upon loss of the GBA gene. Moreover, we tested if reinstating glucocerebrosidase activity by treating cells with our in-house GCase-BS (glucocerebrosidase-brain shuttle) can revert these changes, both at the cellular and lysosomal level.