Potassium two pore domain channel subfamily K member 6 (KCNK6)

Potassium two pore domain channel subfamily K member 6 (KCNK6) is a protein-coding gene encoding a two-pore-domain leak-type potassium ion channel that functions as an open rectifier. It forms functional dimers with each monomer containing two pore-forming domains. This ion channel is widely expressed across tissues including the vascular system and nervous system. It plays a key role in maintaining resting membrane potential by allowing passive efflux ("leak") of potassium ions from cells under physiological conditions. The activity of this protein can be stimulated by arachidonic acid and inhibited by internal acidification as well as volatile anesthetics. In immune cells such as macrophages, it enables ATP-induced activation of the NLRP3 inflammasome during bacterial infection—a process important for innate immunity but also implicated in inflammatory diseases. Abnormal expression levels have been linked to several pathological states including various cancers (breast cancer being notably studied), vascular dysfunctions like pulmonary hypertension when expression is low, pain syndromes related to inflammation in neural tissue, and possibly other disorders involving dysregulated cell excitability or volume control.[2][4][6]

Other names

TRESK (less common, more often used for KCNK18)TWIK-related spinal cord potassium channelPotassium channel subfamily K member 6.2 (variant/alternative name)K2P6.1 (systematic nomenclature)

Drugs or endogenous compounds that modulate this protein typically act by altering the open probability or conductance state of the leak potassium current through the two-pore domain structure—either enhancing outward rectifying currents or inhibiting them to affect cell excitability.