The development of enzyme replacement therapy for lysosomal diseases: Gaucher disease and beyond

The first identification of lysosomes occurred in the late 1950s and early 1960s with the pioneering cell fractionation work of de Duve and co-workers [1]. Lysosomes have been found in almost all mammalian cell types and are composed of a self-limiting lipid membrane enclosing several dozen hydrolytic enzymes required to degrade complex molecules [for review, see Reference 2]. Embedded in the lipid membrane are also found transport proteins, receptors, and ion pumps required to maintain the acidic environment of the organelle. In addition, several small “activator” molecules have been found within lysosomes that influence the activities of specific hydrolytic enzymes.