Pompe disease is an autosomal recessive myopathic disorder caused by the 
deficiency of lysosomal acid α-glucosidase (GAA). Recently, we showed that 
function of mutant GAA in fibroblasts derived from Pompe disease patient 
carrying c.546G>T mutation is improved by treatment with proteasome inhibitor 
bortezomib as well as pharmacological chaperone (PC). However, 
bortezomib-responsive GAA mutations are not fully characterized. In this study, 
we showed the effect of bortezomib on different mutants of GAA in patient 
fibroblasts and transiently expressed HEK293T cells. Bortezomib increased the 
maturation and residual activity of GAA in patient fibroblasts carrying 
PC-responsive M519V and PC-unresponsive C647W mutations. Enhanced colocalization 
of GAA with lysosomal marker LAMP2 was also observed in patient fibroblasts 
after treatment with bortezomib. When four distinct mutant GAAs, which show 
different response to PC, were overexpressed in HEK293T cells, bortezomib 
improved the activity of M519V, S529V, and C647W in them (1.3-5.9-fold). These 
results indicate that bortezomib enhances the activity of some PC-unresponsive 
GAA mutants as well as PC-responsive mutants.