Kcnk2, also known as TREK1, is a member of the two-pore domain potassium (K2P) channel family. It is crucial for maintaining cellular membrane resting potentials. Kcnk2 can be gated by various stimuli such as mechanical stretch, polyunsaturated fatty acids, and intracellular acidification [5]. It is involved in multiple biological processes including those related to the central nervous system (CNS), where it regulates immune-cell entry and CNS inflammation [4].

In esophageal squamous cell carcinoma (ESCC), miR-132-3p promotes tumorigenesis by targeting Kcnk2. Knockdown of Kcnk2 promotes ESCC progression in vitro, suggesting its role as a potential tumor suppressor in this context [1]. In spinal cord ischemia-reperfusion injury, the transcription factor Foxd3 potentiates miR-214-dependent inhibition of Kcnk2. Overexpression of Kcnk2 enhances cell viability and inhibits apoptosis of PC12 cells under hypoxia/reoxygenation conditions, indicating its protective role in this injury [2]. In pulmonary arterial hypertension, up-regulated expression of Kcnk2 facilitates the proliferation and migration of pulmonary arterial smooth muscle cells via enhanced Ca2+ and JNK signaling pathways, contributing to vascular remodeling [3].

In conclusion, Kcnk2 plays essential roles in maintaining membrane resting potential and is involved in various disease-related biological processes. Findings from studies like those on ESCC, spinal cord ischemia-reperfusion injury, and pulmonary arterial hypertension, which likely involved in vivo models including potential KO/CKO mouse models, highlight its significance in these disease areas, offering potential therapeutic targets.