KCNK2 (also named TWIK-related K⁺ channel, TREK-1 or K_2P2.1) is a member of the 2-pore (2P) domain K⁺ channels family that includes at least 16 members. These channels show little time- or voltage-dependence and are considered to be “leak” or “background” K⁺ channels, thereby generating background currents which help set the membrane resting potential and cell excitation.

The K_2P channels have a signature topology that includes four transmembrane domains and two pore domains with intracellular N- and C- termini. 

K_2P channels are regulated by diverse physical and chemical stimuli including temperature, changes in intracellular pH, mechanical stretch, inhalation anesthetics, etc. The channels can then be subclassified based in their specific activators. KCNK2 can be integrated to a K_2P subfamily that includes K_2P4.1 (TRAAK) and K_2P10.1 (TREK2) that are activated by intracellular unsaturated fatty acids such as arachidonic acid, lysophosphatidic acid and mechanical stretch. In addition, KCNK2 can also be activated by general anesthetics such as halothane and chloroform and intracellular acidification.

KCNK2 expression in humans is largely restricted to the brain with some expression in ovary and small intestine while KCNK2 expression in rodents is more widespread.

KCNK2 has an important role in mood regulation, as knockout mice show resistance to depression, suggesting that KCNK2 may be a potential target for anti-depressants.

KCNK2 is involved in the fast release of glutamate from astrocytes. It requires the activation of G_αi, dissociation of G_βγ, followed by the opening of the glutamate permeable KCNK2 (TREK-1) K⁺ channel through its interaction with G_βγ. For this purpose, KCNK2 is localized at the cell surface of the cell body and processes of astrocytes.