Downstream of TNFR1, following the formation and dissociation of complex II, activated caspase-8 will cleave RIPK1 and possibly RIPK3, preventing the formation of a second cytolosolic complex, the Necrosome. RIPK1 containing death complexes can also form downstream of FAS and TRAIL and the pattern recognition receptors. Complete inhibition of caspase-8 enables recruitment and phosphorylation of RIPK3 forming the necrosome. Necrosomes can also form independent of RIPK1 via complexes involving other RHIM domain-containing proteins such as ZBP1 upon detecting dsRNA within the cell, or TRIF via endosomal TLR3 or membrane-bound TLR4. Phosphorylated RIPK3 phosphorylates and activates MLKL. Activated MLKL oligomerises and translocates to the cell membrane, generating pores that result in the release of cell contents, cellular swelling and rupture, and the highly inflammatory necroptotic death of the cell.