Figure 1. The evolution of the knowledge on LSDs.

After the identification of the first clinical phenotypes during of the 19th century, the knowledge on LSDs evolved following the recognition of lysosomes in 1955/56 and the demonstration of the biochemical defects underlying LSDs, starting from 1963. Between the 1970s and 1990s, research in this field was focused on the mannose‐6‐phosphate receptor pathway and on the mechanisms underlying the sorting of lysosomal enzymes, on the identification of the molecular bases of LSDs, and on the development of tools and strategies to investigate lysosomal biology. The first attempts to treat these disorders by enzyme replacement therapy started in the 1990s. Current research is now focusing on the role of lysosomes as signaling platforms controlling cellular metabolism and on the development of new therapeutic approaches.