Mapping where and when necroptotic cell death occurs in disease.

A series of recent studies have established where the necroptosis machinery — RIPK1, RIPK3, MLKL, ZBP1 and Caspase-8 — occur and are activated in mouse and human tissues, and how ZBP1 splicing might regulate necroptosis. These studies highlight the importance of mapping necroptosis spatially to understand how pathway dysregulation can lead to disease.