TRESK: The lone ranger of two-pore domain potassium channels

► TRESK is a K2P potassium channel regulated by cytoplasmic Ca2+ concentration. ► The calcium/calmodulin-regulated phosphatase calcineurin activates the channel. ► TRESK is primarily expressed in the sensory neurons of DRG and trigeminal ganglia. ► Dominant negative mutation of the human channel is linked to migraine with aura. ► TRESK has a role in the trigeminovascular system or in cortical spreading depression.