It is evident that the gasdermin family is central to pyroptosis. This is because the gasdermin family members are the executioners of pyroptosis, and their pore-forming function is a necessary condition for pyroptosis to occur. This family generally includes a cytotoxic N-terminal domain and a C-terminal inhibitory domain. After cleavage, the N-terminal domain is released and can assemble into pores in the membrane. Gasdermin pores disrupt the integrity of the cell membrane, leading to inflammatory cell death, with cell contents, including inflammatory cytokines, being released into the extracellular space.

Although the phenomenon of cell death had been known for centuries, even briefly described in the 19th century, the explosion of research and technology in the latter half of the 20th century led to greater and more nuanced discoveries that have provided insights into many physiological processes including tissue development, maintenance, metabolism, and disease states including cancer. The many accomplishments in programmed cell death research have improved our understanding and development of targeted therapeutics, and some of these milestones were recognized by Nobel Prizes for apoptosis and autophagy. As scientists continue to elucidate new cell death pathways and their interplay with other pathways, let's take a look at what we know so far and what new findings have come out.

Once upon a time when I was a fledgling science nerd in high school, I started learning about the process of apoptosis, which remains to this day the most studied form of cell death in various functions including organismal development and defense against cancer. As an immunologist-in-training, I also learned about the classical complement pathway that the immune system uses to destroy infected cells, and also necrotic cell death or necroptosis (which is full of really gross pictures if you dare to Google it). Of course, I learned about autophagy in graduate school and really appreciate its utility in normal physiology and disease, while very recently I read about ferroptosis as yet another programmed cell death (PCD) pathway. Right around when the Nobel Prize was awarded to recognize the elucidation of PCD, pyroptosis came about as a novel PCD pathway that is continuing to gain steam in its clinical relevance. It seems logical for cells and organisms to have redundant systems in place to clear away damaged and malignant cells before a health crisis can emerge if the cell evades the primary route of apoptosis.