Although UPS activation was confirmed in our study and the autophagic nature of these vacuoles is supported by the observations of acid-phosphatase rich primary lysosomes, clathrin-positive granules, and the presence of cathepsins B and L in GNE myopathy [29], how the two proteolytic pathways are regulated is still an unsolved problem. The gene discussed is CTSB; the disease is Distal myopathy, Nonaka type.