In our study, abundant VCP in muscle tissue from GNE myopathy patient indicated an enhanced delivery process of misfolded proteins from endoplasmic reticulum to cytosol.We also found significantly increased activities of three major proteasomal proteolytic enzymes accompanied by the up-regulation of 20S proteasome subunits both on protein and mRNA levels, indicating UPS is activated to eliminate unfolded proteins in GNE myopathy muscle. Here, VCP is linked to GNE myopathy.