Dipeptidyl peptidase 10 (DPP10, DPPY) is a member of the prolyl oligopeptidase family (shares a 30% sequence identity with DPP4) and belongs to the S9B serine protease subfamily. DPP10 is a homologous glycosylated, single-pass type II transmembrane protein that lacks the crucial serine residue of the catalytic triad. Unlike other K_V4 subunits such as DPP6, DPP10 has a restricted expression pattern including the brain, adrenal gland and pancreas.  The presence of DPP10 in endocrine cells suggests that the protein may also have an additional function related to the regulation of hormone secretion. DPP10 accelerates the activation and inactivation of K_V4.3 channel gating with distinct biophysical properties.

DPP10 associates with the α-subunits of the K_V4 subfamily to form a ternary complex of approximately 750 kDa¹. In addition, DPP10 forms complexes with other auxiliary subunits of the K_V4 channels. In dorsal root ganglion DPP10 is co-localized with K⁺ channel-interacting proteins 1 and 2 (KChIPs) in the somatic surface and cytoplasm of K_V4.3 nociceptors. Recently it has been hypothesized that K_V4/KChIP/DPPL ternary complexes exist in subthreshold A-type K⁺ currents (Isas) expressing nociceptors and pain-modulating spinal interneurons².

DPP10 has been implicated in various pathologies. Aggregation of the protein is associated with neurodegenerative conditions such as Alzheimer’s, diffuse Lewy body disease and fronto-temporal dementia³.