KCNK9, also known as TASK3, encodes a member of the two pore-domain potassium channel (K2P) subfamily. It regulates intracellular calcium concentration, thus modulating cell survival and inflammatory signaling pathways. It is involved in genomic imprinting, with the gene normally imprinted with paternal silencing [3].

KCNK9 deficiency in Kcnk9 -/- mice led to aggravated dextran sulfate sodium (DSS)-induced colitis, as intestinal epithelial cells showed increased intracellular calcium levels, more mitochondrial damage, and caspase-9-dependent apoptosis. KCNK9 enhances mitochondrial stability, reduces apoptosis, and supports epithelial cell survival after DSS exposure in vivo and in vitro. Also, in colon cancer, KCNK9 was overexpressed, and its down-regulation or the application of genistein could suppress cell proliferation, migration, invasion, induce cell cycle quiescence, promote apoptosis, and reduce epithelial-mesenchymal transition. Genistein could inhibit KCNK9 expression, attenuating the Wnt/β-catenin signaling pathway [2,1].

In conclusion, KCNK9 plays a crucial role in maintaining cell survival, especially in intestinal epithelial cells, by regulating calcium levels and apoptosis. In disease conditions, such as colon cancer and colitis, its function is dysregulated. Studies using Kcnk9 -/- mouse models have revealed its significance in these disease areas, providing insights into potential therapeutic strategies.