Researchers have discovered that polo-like kinase 1 (PLK1) inhibitors may reduce NLR family pyrin domain–containing 3 (NLRP3) inflammasome–elicited responses in patients with inflammatory diseases such as cardiovascular disease and gout, according to a novel study published by Baldrighi et al in The Journal of Clinical Investigation. Researchers used an unbiased proximity-dependent biotin identification screen to analyze the PLK1 interactome in macrophages. They demonstrated that PLK1 may trigger NLRP3 inflammasome activation during cell interphase. Upon activation, PLK1 orchestrated the microtubule-organizing center structure and NLRP3 subcellular positioning. However, in inflammatory mouse models—including lipopolysaccharide-induced endotoxemia and monosodium urate–induced peritonitis—the researchers were able to suppress interleukin-1 beta production with selective PLK1 inhibitors. The researchers underscored that PLK1 may play a critical role in regulating NLRP3 inflammasome activation and hope their new findings can lead to a novel therapeutic strategy to treat cardiovascular disease and gout. In a companion press release on the findings from the University of Cambridge, the study authors concluded: “If we can get in the way of the microtubules as they try to organize themselves, then we can in effect slow down the inflammatory response, preventing it from causing collateral damage to the body [and] … preventing a number of common diseases that can cause pain, disability, and in some cases … life-threatening complications.”