Abstract Welander distal myopathy (WDM) is a dominant late-onset muscular dystrophy affecting primarily the extensor muscles of the fingers, and progressing later to involve lower leg and all hand muscles. The muscle histopathology in WDM shows variable myopathic–dystrophic changes in the affected muscles with frequent rimmed vacuoles and autophagic degenerative pathology on electron microscopic examination. We have analyzed WDM muscle biopsies using immunohistochemistry, immunofluorescence and Western blotting to further elaborate which molecular pathways are affected in WDM. We have assessed the expression of the proteins involved in the autophagosomal–lysosomal pathway (LAMP2, Cathepsin B and LC3), the ubiquitin–proteasome-mediated protein degradation pathway and VCP, the linker between these pathways. In addition, we used common markers (SMI31, p62 and TDP-43) of the rimmed vacuolar pathologies such as s-IBM. Our results suggest that there is an increase of misfolded or aggregated, partly ubiquitinated proteins as shown with increase of sequestosome (p62), TDP-43 and SMI31 both in the rimmed vacuolar regions and patchy in all atrophic fibers. This is accompanied with activation of the autophagic system as judged by some increase of LAMP2 positive regions that are too large to represent normal mature lysosomes. In contrast, the rimmed vacuoles are more or less devoid of LAMP2 positive mature lysosomes, and are instead filled with LC3-positive autophagosomes. The primary mutation in WDM causes a downstream abnormality including both incapacity of the proteasomal system to degrade all ubiquitinated proteins, and apparent decompensation of the autophagic system despite its activation.