Intrinsic and extrinsic apoptotic signals are received and converge at the activation of caspase 3/7. Caspase 3-cleaved GSMDE and NINJ1 may facilitate the progression to secondary necrosis. Primary necrosis is traditionally stochastic in nature resulting in uncontrolled membrane rupture. In the presence of caspase inhibition, TNF-α can induce necroptosis through binding the TNF-R which results in the activation of RIPK1/3 and formation MLKL pores at the membrane. Pyroptosis is mediated via either the canonical (caspase 1) or non-canonical (caspase 4/5/11) pathway which converge with the formation of GSDMD membrane pores.