Regulated necrosis: the expanding network of non-apoptotic cell death pathways

Cell death research was revitalized by the understanding that necrosis can occur in a regulated and genetically controlled manner. Although necroptosis is the most recognized form of regulated necrosis, other examples of this process have emerged. Understanding how these pathways are interconnected should enable regulated necrosis to be therapeutically targeted. Cell death research was revitalized by the understanding that necrosis can occur in a highly regulated and genetically controlled manner. Although RIPK1 (receptor-interacting protein kinase 1)- and RIPK3–MLKL (mixed lineage kinase domain-like)-mediated necroptosis is the most understood form of regulated necrosis, other examples of this process are emerging, including cell death mechanisms known as parthanatos, oxytosis, ferroptosis, NETosis, pyronecrosis and pyroptosis. Elucidating how these pathways of regulated necrosis are interconnected at the molecular level should enable this process to be therapeutically targeted.