DPP6 is an auxiliary subunit of voltage-gated potassium channels (particularly KCND2/Kv4) that regulates neuronal excitability through two primary mechanisms. First, DPP6 promotes cell surface expression of KCND2 and modulates its gating characteristics 12, interacting with the voltage-sensing domain S1-S2 helices to accelerate voltage-dependent channel activation 3. Second, DPP6 has an independent role in synaptic development and maintenance, regulating dendritic filopodia formation 4. Despite possessing structural similarity to dipeptidyl peptidases, DPP6 lacks enzymatic activity 5. DPP6 dysfunction is implicated in multiple neurological disorders. DPP6 knockout mice exhibit impaired hippocampal-dependent learning and memory with reduced brain size 6. Aging DPP6-deficient mice develop Alzheimer's disease-like pathology, including amyloid-β and phosphorylated tau accumulation, neuroinflammation, and circadian dysfunction 7. The DPP6 rs10260404 polymorphism is associated with increased sporadic amyotrophic lateral sclerosis risk in Caucasian populations 8. Additionally, DPP6 genetic variants have been associated with tardive dyskinesia in schizophrenia patients 9. These findings establish DPP6 as a multifunctional protein critical for both ion channel regulation and synaptic homeostasis, with dysfunction contributing to neurodegenerative and neuropsychiatric disease pathogenesis.