Dipeptidyl-peptidase 6 (DPP6) is a type II membrane glycoprotein¹ which is a part of the dipeptydil aminopeptidase-like proteins (DPPLs) subfamily. It is an auxiliary glycoproteinic subunit of voltage-dependent K⁺ channel 4 (K_V4.x), that has a short cytoplasmic domain, a long extracellular domain and a transmembrane domain. It regulates sub-threshold, A-type K⁺ currents, and is important for the enhancement and localization of K_V4.2 channels².

DPPLs are a subgroup of the larger prolyl oligopeptidase family. A loss-of-function mutation at their enzymatic serine renders them incapable of cleaving peptides. Notable DPPLs include DPP8, DPP9, and DPPIV – the latter is known to regulate several key functions in varied systems, ranging from immune to CNS^1,3.

Alternative mRNA splicing of the DPP6 gene (part of the di-genic DPLP group that also consists DPP10) gives rise to several isoforms that differ in their N-terminal (DPP6a, DPP6K, DPP6S, DPP6L DPP6E)⁴.

DPP6 proteins are widely expressed throughout both of the nervous systems – albeit much more predominantly in the CNS - and are known to play a major role in neurogenesis and neurodevelopment⁵.

Deletion mutations and haplo-insufficiency of the DPP6 gene has been shown to be associated with autism spectrum disorder, Gilles de la Tourette syndrome, dominant microcephaly and mental retardation^5,6. Endometriosis – a condition characterized by extra-uteral endometrial glands that affects one tenth of fertile women population – has been linked with DPP6 in genome wide associations studies (GWASs)⁷.