Pompe disease (glycogen storage disease type II) is an autosomal recessive myopathic disorder arising from the deficiency of lysosomal acid a-glucosidase (GAA). Recently, we found that mutant GAA in patient fibroblasts carrying c.546G > T mutation is stabilized by treatment with proteasome inhibitor as well as pharmacological chaperon N-butyl-deoxynojirimycin. In this study, we characterized the effect of two proteasome inhibitors, bortezomib and MG132, on maturation, subcellular localization and residual activity of mutant GAA in the patient fibroblasts carrying c.546G > T mutation. Each proteasome inhibitor promoted the stabilization of patient GAA and processing of them to mature forms without cytotoxic effect. Immunocytochemical analysis showed increased colocalization of GAA with the lysosomal marker LAMP2 in patient fibroblasts treated with proteasome inhibitors. Furthermore, bortezomib and MG132 also increased enzyme activity in the patient fibroblasts (about 4-fold and 2-fold, respectively). These findings indicate that proteasome inhibitor may be a novel drug as potential pharmacological chaperone therapy for Pompe disease patient carrying chaperon-responsive mutation. (C) 2011 Elsevier Inc. All rights reserved.