Asparagine endopeptidase (AEP)

Asparagine endopeptidase (AEP) is a lysosomal cysteine protease primarily responsible for cleaving peptide bonds at the C-terminus of asparagine residues. Encoded by the LGMN gene in humans, AEP (also called legumain or δ-secretase) is involved in protein and peptide degradation predominantly in late endosomes and lysosomes[1][3][5]. It plays crucial roles in antigen processing, regulation of cell death, and maturation of immune receptors such as TLRs[1][4]. AEP is tightly regulated by pH, remaining inactive at neutral pH and becoming activated under acidic conditions typical of lysosomes[1][2][5]. Dysregulation of AEP activity has been implicated in various pathologies, notably neurodegenerative diseases like Alzheimer’s and Parkinson’s (through cleavage of tau, amyloid precursor protein, and SET protein), certain cancers, stroke, and chronic inflammation[2][3][4]. While there are no approved drugs directly targeting AEP, selective inhibitors are being explored in preclinical models for their potential therapeutic benefits[3][4][5].

Other names

legumainδ-secretaseasparaginyl endopeptidaseLGMN gene productPRSC1 gene productmammalian legumainproteinase Bhemoglobinasecitvacvicilin peptidohydrolasebean endopeptidase (context-dependent, especially in plants)

Competitive or irreversible inhibition of the AEP catalytic cysteine site, preventing substrate cleavage at asparagine residues