Mammalian legumain – A lysosomal cysteine protease with extracellular functions?

The cysteine protease legumain (asparaginyl endopeptidase, AEP) plays important roles in normal physiology but is also associated with several disorders, such as atherosclerosis, osteoporosis, cancer and neurodegenerative diseases. The functional roles of legumain have mainly been associated with the presence in lysosomes where legumain is active and mediates processing of multiple proteins, such as the conversion of single to double chain forms of cysteine cathepsins. However, in recent years, a number of studies point to extracellular roles of legumain in addition to the pivotal roles in the lysosomes. In this review, recent knowledge on novel extracellular functions of this protease will be addressed and new discoveries in relation to the diseases mentioned above will be presented.