Lysosomal storage diseases are inborn errors of metabolism, the hallmark of which is the accumulation, or storage, of macromolecules in the late endocytic system. They are monogenic disorders that occur at a collective frequency of 1 in 5,000 live births and are caused by inherited defects in genes that mainly encode lysosomal proteins, most commonly lysosomal enzymes. A subgroup of these diseases involves the lysosomal storage of glycosphingolipids. Through our understanding of the genetics, biochemistry and, more recently, cellular aspects of sphingolipid storage disorders, we have gained insights into fundamental aspects of cell biology that would otherwise have remained opaque. In addition, study of these disorders has led to significant progress in the development of therapies, several of which are now in routine clinical use. Emerging mechanistic links with more common diseases suggest we need to rethink our current concept of disease boundaries.
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Thanks to D. Priestman for creating Fig. 1 and to N. Platt for his comments on the manuscript. F.M.P is a Royal Society Wolfson Research Merit Award holder.
F.M.P. is a consultant for Actelion and Orphazyme.
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Platt, F. Sphingolipid lysosomal storage disorders. Nature 510, 68–75 (2014). https://doi.org/10.1038/nature13476
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