Isoform DPPX-S of A-type potassium channel modulatory protein DPP6

DPP6 (dipeptidyl-peptidase-like protein 6) encodes a potassium channel modulatory protein that functions as an A-type K+ channel regulator. This isoform (DPPX-S, UniProt: P42658-2) is a 803 amino acid variant involved in modulating voltage-gated potassium channel activity and neuronal excitability (UniProt: P42658-2).

DPP6 is expressed in neural tissues where it plays roles in regulating neuronal excitability and synaptic function through its interaction with potassium channels. The protein localizes to multiple subcellular compartments including membrane and cytoplasmic fractions, consistent with its role in channel modulation (Chaparral AD proteomics).

In Alzheimer's Disease, DPP6-S is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of −0.62 (Chaparral AD proteomics). This reduction was observed in TMT-labeled proteomic analysis across subcellular fractions from human post-mortem brain. The downregulation of this potassium channel modulator may contribute to altered neuronal excitability patterns characteristic of AD pathology.