Proliferative versus apoptotic functions of caspase-8

► We discuss the emerging role of the caspase-8 in cellular survival and activation. ► Caspase-8 homodimer is pro-apoptotic; the heterodimer with FLIPL is pro-survival. ► Control of RIPK1 activity is an essential function of caspase-8. ► Heterodimer in complex with FADD and RIPK1 activates NF-κB, only if FLIPL is cleaved. ► Further cleavage of the caspase-8 inter-subunit linker turns the heterodimer pro-apoptotic.