Dipeptidyl aminopeptidase-like protein 6 (DPP6) (DPP6)

Dipeptidyl aminopeptidase-like protein 6 (DPP6) is a type II transmembrane protein that belongs to the dipeptidyl peptidase family, although it lacks proteolytic activity due to the absence of essential catalytic residues. It primarily functions as a regulatory subunit of Kv4-family voltage-gated potassium channels, significantly influencing their expression, trafficking, and biophysical properties in neurons and pancreatic islet cells. In the context of immunotherapy, DPP6 has emerged as a novel cell-surface antigen for targeting regulatory T cells (Tregs) to specific tissues. Specifically, CAR-ThyTreg cells (thymic-derived Tregs engineered with a CAR) targeting DPP6 are being investigated for the treatment of autoimmune diseases like Type 1 diabetes, where they can be directed to pancreatic islets to suppress the localized inflammatory response. Beyond its role in the pancreas, DPP6 is highly expressed in the brain, and its dysfunction or autoantibody targeting is associated with neurodegenerative and neuro-autoimmune conditions such as amyotrophic lateral sclerosis (ALS) and autoimmune encephalitis.

Other names

Dipeptidyl peptidase 6Dipeptidyl peptidase VIDPP VIDipeptidyl aminopeptidase-like protein 6DPL1

Targeting of DPP6-expressing cells (such as pancreatic islets or specific neurons) by chimeric antigen receptor (CAR) modified regulatory T cells (Tregs) to induce localized immune tolerance and suppress autoimmune destruction.