Lysosomal storage disorders (LSDs) highlight the diverse ways in which the failure of a single organelle can bring cells to their knees. Most are rare and poorly understood, making the development of therapies a daunting task.
Many moving parts
The lysosome uses specialized enzymes to help cells to digest external biological materials and recycle defective proteins and damaged cellular machinery. Many LSDs arise from mutations in the genes that encode those enzymes, but there are numerous other ways in which this process can break down (red stars).

Potential roads to recovery
The past 25 years have seen considerable progress in the development of treatments that can improve the quality of life for some patients. Most treatments focus on changing intracellular processes. The exception is bone-marrow transplant, in which the patient receives an entire set of healthy stem cells from a suitable donor.

Collectively common, individually rare
LSDs are not especially rare; estimates suggest that 1 in just over 5,000 newborns will be affected. However, each individual disease occurs with much lower frequency — the most common, Gaucher’s disease, affects only 1 in 40,000 newborns worldwide, and the rarest have been described only a handful of times. The diseases shown are those for which there are most data. Numbers have been estimated and are approximate.

The long road to discovery
The first LSDs were identified more than 80 years before researchers were able to identify the cellular structures involved. Since then, new LSDs have been identified along with, more recently, the genes involved and drugs that help to repair the damage.

Sources US National Institute of Neurological Disorders and Stroke; Genetics Home Reference/National Library of Medicine; www.omim.org; www.orpha.net; Gene Reviews; Medscape
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Eisenstein, M. Myriad maladies. Nature 537, S146–S147 (2016). https://doi.org/10.1038/537S146a
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DOI: https://doi.org/10.1038/537S146a