KCNK2 (TREK-1) is a two-pore domain potassium channel that plays critical roles in maintaining cellular membrane potential and regulating diverse physiological processes. The channel functions as a background potassium conductor essential for resting membrane potential maintenance 1. KCNK2 exhibits mechanistic complexity, with certain isoforms lacking channel activity but instead reducing the activity and surface expression of functional isoforms. The channel demonstrates significant involvement in neurological disorders, particularly depression, where genetic polymorphisms in KCNK2 associate with major depressive disorder susceptibility and antidepressant treatment response 2. In vascular physiology, KCNK2 regulates blood-brain barrier function, with downregulation during inflammation facilitating lymphocyte migration 3. The channel also influences matrix metalloproteinase expression in pregnancy-induced hypertension, affecting uterine arterial function 4. KCNK2 shows therapeutic potential in inflammatory conditions, as its activation reduces influenza-induced lung injury through anti-inflammatory effects 5. In cancer biology, KCNK2 expression correlates with tumor progression in thyroid carcinoma and serves as a prognostic biomarker 6. The channel is also expressed in ovarian tissues, where modulators affect cell proliferation and apoptosis 7, and heat-induced downregulation via miR-132-3p promotes esophageal cancer development 8.