Tripeptidyl-peptidase 2 is an enzyme that in humans is encoded by the TPP2gene. Among other things it is heavily implicated in MHC (HLA) class-I processing, as it has both endopeptidase and exopeptidase activity.
Clinical significance and genetic deficiency
Biallelic deleterious variants in the TPP2 gene may result in a recessive disorder with immune deficiency, autoimmune disease and intellectual disability. Some genetic variants may result in a milder disease with sterile brain inflammation mimicking multiple sclerosis. These observations underline the fundamental role of TPP2 in cells of the immune system.
TRIANGLE disease is a rare genetic disorder of the immune system. TRIANGLE stands for "TPPII-related immunodeficiency, autoimmunity, and neurodevelopmental delay with impaired glycolysis and lysosomal expansion" where TPP2 is the causative gene. This disease manifests as recurrent infection, autoimmunity, and neurodevelopmental delay. TRIANGLE disease was first described in a collaborative study by Dr. Helen C. Su from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Dr. Sophie Hambleton from the University of Newcastle and their collaborators in 2014. The disease was also described by the group of Ehl et al.
