The canonical pathway is triggered by tumor necrosis factor receptor (TNFR) superfamily activation, wherein TNF-α binding to TNFR1, coupled with caspase-8 inhibition (as occurs during viral infection or pharmacological intervention), facilitates RHIM domain-mediated interaction between RIPK1 and RIPK3 to form the necrosome complex. Here, TNFRSF1A is linked to viral infectious disease.