Gsdmd, short for gasdermin D, is a key executor protein in pyroptosis, a form of programmed cell death. Inflammatory caspases (such as caspase-1,-4,-5, and-11) can cleave Gsdmd, which is crucial for innate defenses, and this cleavage determines pyroptotic cell death. The process is involved in inflammasome-mediated immunity and diseases, changing our understanding of pyroptosis and programmed necrosis [1].

Genetic KO of Gsdmd in mice alleviated depression-like behaviors and inhibited pyroptosis-associated protein expression, suggesting that NLRP3/caspase-1/Gsdmd-mediated pyroptosis plays a crucial role in astrocyte pathological injury in a mouse model of depression [2]. In obstructive nephropathy, Gsdmd deletion in neutrophils protected the kidney from fibrosis, as Gsdmd-dependent neutrophil extracellular traps promoted macrophage-to-myofibroblast transition and renal fibrosis [3].

In conclusion, Gsdmd is essential in the process of pyroptosis, playing a significant role in various disease conditions such as depression and renal fibrosis. Studies using Gsdmd KO mouse models have been instrumental in revealing its functions in these disease areas, providing insights into potential therapeutic strategies targeting pyroptosis-related pathways.