DPP10 is a new regulator of Nav1.5 channels in human heart.

•Accessory β-subunits associate with the depolarizing Nav1.5 channel and the repolarizing Kv4.3 channel in human heart.•We discovered DPP10 as a new regulator of Nav1.5 channels by co-immunoprecipitation in human heart.•DPP10 altered voltage-dependence of Na+ current and upstroke velocity of action potential in rat epicardial cardiomyocytes.•DPP10 represents a novel functional link between the cardiac Na+ and K+ channels.•Being upregulated in heart failure, DPP10 might contribute to the development of cardiac arrhythmias.