Tripeptidyl-peptidase II (TPP2)

Tripeptidyl-peptidase II is a giant cytosolic serine protease, assembling into a spindle-shaped, homo-oligomeric complex of up to 6 MDa[1][2][3]. Its primary function is to cleave tripeptides from the N-termini of longer peptides, especially those generated by proteasomes, thus contributing to amino acid recycling and the processing of antigenic peptides for immune presentation[1][3]. TPP2 is crucial for cellular and immune homeostasis: its deficiency causes immune system aging and autoimmunity, while its overexpression promotes proliferative and malignant behaviors—particularly through interactions with cell cycle regulators such as p53 and CDK2[1]. TPP2 is also implicated in metabolic regulation, acting as a backup proteolytic route for the proteasome and supporting viral propagation when proteasomal degradation is impaired[1]. Structurally, TPP2 features a subtilisin-like catalytic domain and forms long, twisted oligomers with internal cavities[2][3]. Although no clinical drugs target TPP2 directly, the enzyme is a research target in cancer, apoptosis, immune, and infection biology[1][3].

Other names

Tripeptidyl peptidase IITPP2TPP-2TPPIITripeptidyl aminopeptidaseIMD78

Inhibitors block protein degradation and antigen processing, potentially triggering apoptosis or altering immune responses. AAF-CMK acts as a covalent inhibitor of serine proteases