The non-functional dipeptidyl peptidase, DPPY (DPP 10), regulates the expression and gating of K+ channels in Kv4 family by tightly binding to these pore-forming subunits. Neural tissue-specific expression of this and the related DPPX (DPP6) is thought to confer rapid inactivation and other unique properties of neuronal Kv4 channels. Here we report that DPPY mRNA is abundant in human adrenal gland, but very low in the corresponding rat tissue. Furthermore, multiple DPPY splicing variants with alternative first exons are significant in the brain, whereas the expression of DPPY gene in the adrenal gland and pancreas is predominantly initiated at the two latter sites. These splicing variants, as well as an N-terminal peptide-deleted DPPY, produce similar changes in Kv4.3 gating. Thus, transcription of DPPY gene is species- and tissue-specifically controlled. (c) 2006 Elsevier Inc. All rights reserved.