Since the discovery of the lysosome in 1955, advances have been made in understanding the key roles and functions of this organelle. The concept of
lysosomal storage diseases (LSDs)--disorders characterized by aberrant, excessive storage of cellular material in lysosomes--developed following the discovery of α-
glucosidase deficiency as the cause of
Pompe disease in 1963. Great strides have since been made in understanding the pathobiology of LSDs and the
neuronal ceroid lipofuscinoses (NCLs). The NCLs are
neurodegenerative disorders that display symptoms of cognitive and motor decline,
seizures,
blindness, early death, and accumulation of
lipofuscin in various cell types, and also show some similarities to 'classic' LSDs. Defective lysosomal storage can occur in many cell types, but the CNS and PNS are particularly vulnerable to LSDs and NCLs, being affected in two-thirds of these disorders. Most LSDs are inherited in an autosomal recessive manner, with the exception of X-linked Hunter disease,
Fabry disease and
Danon disease, and a variant type of adult NCL (
Kuf disease). This Review provides a summary of known LSDs, and the pathways affected in these disorders. Existing
therapies and barriers to development of novel and improved treatments for LSDs and NCLs are also discussed.