The family of gasdermin proteins plays a key role in the host response against external and internal pathogenic signals by mediating the form of inflammatory regulated cell death known as pyroptosis. ...One of the most well-studied gasdermins within innate immunity is gasdermin D, which is cleaved, oligomerizes, and forms plasma membrane pores. Gasdermin D pores lead to a number of downstream cellular consequences including plasma membrane rupture, or cell lysis. In this review, we describe mechanisms of activation for each of the gasdermins, their cell type specificity and some disease associations. We then discuss downstream consequences of gasdermin pore formation, including cellular mechanisms of membrane repair. Finally, we present some important next steps to better understand pyroptosis and the cellular consequences of gasdermin pore formation.
•The definition of 'pyroptosis' has evolved from caspase-1- to gasdermin-mediated cell death.•Multiple proteins in the gasdermin family have been identified, some leading to pyroptosis.•Different mechanisms regulate gasdermin pore formation, repair, and cargo release.•Cellular consequences of gasdermin pores alter the intracellular environment.
