Necroptosis in development, inflammation and disease

Nat Rev Mol Cell Biol. 2017 Feb;18(2):127-136. doi: 10.1038/nrm.2016.149. Epub 2016 Dec 21.


In the early 2000s, receptor-interacting serine/threonine protein kinase 1 (RIPK1), a molecule already recognized as an important regulator of cell survival, inflammation and disease, was attributed an additional function: the regulation of a novel cell death pathway that came to be known as necroptosis. Subsequently, the related kinase RIPK3 and its substrate mixed-lineage kinase domain-like protein (MLKL) were also implicated in the necroptotic pathway, and links between this pathway and apoptosis were established. In this Timeline article, we outline the discoveries that have helped to identify the roles of RIPK1, RIPK3, MLKL and other regulators of necroptosis, and how they interact to determine cell fate.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Caspase 8 / metabolism
  • Cell Death
  • Disease Models, Animal
  • Humans
  • Inflammasomes / metabolism
  • Inflammation / metabolism
  • Inflammation / pathology*
  • Necrosis / pathology*
  • Necrosis / physiopathology
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Receptor-Interacting Protein Serine-Threonine Kinases / genetics
  • Receptor-Interacting Protein Serine-Threonine Kinases / metabolism


  • Inflammasomes
  • MLKL protein, mouse
  • Protein Kinases
  • Receptor-Interacting Protein Serine-Threonine Kinases
  • Ripk1 protein, mouse
  • Ripk3 protein, mouse
  • Caspase 8