The Mammalian Cysteine Protease Legumain in Health and Disease

Rigmor Solberg*, Ngoc Nguyen Lunde, Karl Martin Forbord, Meshail Okla, Moustapha Kassem, Abbas Jafari


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The cysteine protease legumain (also known as asparaginyl endopeptidase or δ-secretase) is the only known mammalian asparaginyl endopeptidase and is primarily localized to the endolysosomal system, although it is also found extracellularly as a secreted protein. Legumain is involved in the regulation of diverse biological processes and tissue homeostasis, and in the pathogenesis of various malignant and nonmalignant diseases. In addition to its proteolytic activity that leads to the degradation or activation of different substrates, legumain has also been shown to have a nonproteolytic ligase function. This review summarizes the current knowledge about legumain functions in health and disease, including kidney homeostasis, hematopoietic homeostasis, bone remodeling, cardiovascular and cerebrovascular diseases, fibrosis, aging and senescence, neurodegenerative diseases and cancer. In addition, this review addresses the effects of some marketed drugs on legumain. Expanding our knowledge on legumain will delineate the importance of this enzyme in regulating physiological processes and disease conditions.

TidsskriftInternational Journal of Molecular Sciences
Udgave nummer24
Antal sider22
StatusUdgivet - dec. 2022

Bibliografisk note

Funding Information:
This research was funded by the Olav Thon Foundation (MK, AJ, RS, and NNL), the University of Oslo (RS, NNL, and KMF), Gerda og Aage Haenschs Fond (AJ), and Direktør Michael Hermann Nielsens mindelegat (AJ).


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