Legumain

Legumain is a member of the asparaginyl endopeptidase family of proteases, which are enzymes that cleave peptide bonds in proteins. It is primarily expressed in various tissues and organs, including the brain, liver, and reproductive system, with notable roles in physiological and pathological processes. The enzyme is encoded by the *Legumain* gene in humans, located on chromosome 11, and its activity is tightly regulated to prevent unintended proteolysis.

Legumain is characterized by its ability to cleave peptide bonds at the carboxyl side of asparagine residues, particularly in acidic environments. This specificity is crucial for its involvement in processes such as antigen processing, immune regulation, and tissue remodeling. Unlike many other proteases, legumain is synthesized as an inactive proenzyme (prolegumain) and requires activation through autocatalytic cleavage or by other proteases. The activation process is often linked to cellular stress or inflammatory responses.

In the immune system, legumain plays a role in the degradation of proteins within endosomes and lysosomes, contributing to the presentation of antigens on major histocompatibility complex (MHC) class II molecules. This function is essential for adaptive immunity, particularly in antigen-presenting cells like dendritic cells and macrophages. Dysregulation of legumain has been implicated in autoimmune diseases and cancer, where its elevated expression may promote tumor progression or immune evasion.

Additionally, legumain has been studied in the context of neurodegenerative diseases, such as Alzheimer’s disease, where its activity may influence amyloid-beta processing. Research also suggests its involvement in viral replication, as some viruses, including herpes simplex virus and human cytomegalovirus, utilize legumain for efficient infection cycles. Inhibitors of legumain are being explored as potential therapeutic agents for conditions where its activity is detrimental, such as cancer and autoimmune disorders.