Kcnk13, also known as THIK-1, encodes a two-pore potassium channel. This channel is involved in multiple biological functions. It plays a role in regulating microglial ramification, surveillance, and interleukin-1β release, and is also associated with the NLRP3-inflammasome pathway, which is important in inflammation-related processes [4,5].

In animal studies, knockdown of Kcnk13 in rats and mice has shown its significance in alcohol-related behaviors. In rats, knockdown of Kcnk13 using siRNA reduced ethanol-induced excitation of ventral tegmental area (VTA) neurons, and in mice, shRNA-mediated knockdown of Kcnk13 in the VTA increased alcohol drinking, indicating that Kcnk13 can control VTA neuronal activity and binge-like drinking [1,3]. Also, KCNK13 expression was increased by acute ethanol exposure in the VTA of mice [3].

In neurodegenerative diseases, the discovery of CVN293, a brain-permeable KCNK13 inhibitor, suggests that modulation of KCNK13 activity may be a potential treatment strategy, as KCNK13 is specifically expressed in human microglia with elevated expression in post-mortem human brain tissue from Alzheimer's disease patients [2].

In conclusion, Kcnk13 is a crucial gene involved in alcohol-related neuronal excitation and potential treatment of neurodegenerative diseases. Gene knockdown models in rats and mice have been instrumental in revealing its role in these processes, providing valuable insights for understanding the underlying mechanisms and developing potential therapeutic strategies.