Advances in gasdermin activation, regulation, and targeted drug development

Proteins of the gasdermin family are executors of pyroptosis. Upon cleavage-dependent/independent activation, gasdermins form pores on the cell membrane, which damage the integrity of the cell membrane and lead to pro-inflammatory cellular content release and lytic cell death. The role of gasdermin in pyroptosis-associated diseases, such as allergic diseases, neurologic disorders, infections, and cancer, showcases the tremendous therapeutic potential of targeting gasdermin. New insights into non-pyroptotic functions continue to further our understanding of gasdermin. Herein we review current knowledge of the gasdermin family, demonstrating the mechanism of activation, downstream effects, and regulatory mechanisms. We also discuss the association with pyroptosis-associated diseases and the functions beyond pyroptosis, shedding light on the broader roles in various pathologic processes. Furthermore, we summarize the advances in the development of targeted agonists and inhibitors with strategies for developing pyroptosis-based anti-tumor therapies.