Recent studies have revealed that cell death stimuli can trigger programmed necrosis, necroptosis. Receptor-interacting serine–threonine kinase family RIP plays a crucial role in regulating the switch between apoptosis and necroptosis. Two studies now describe a novel RIP1 containing ∼2 MDa ‘Ripoptosome’ complex assembled in the cytosol to mediate both apoptosis and necroptosis in response to genotoxic stress and TLR3 stimulation. Intriguingly, cIAPs and XIAP function as endogenous inhibitors of Ripoptosome by direct ubiquitination of its components.
