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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily. TRAIL activates apoptosis through the death receptors DR4 (also known as TRAILR1 and TNFRSF10A) and DR5 (also known as TRAILR2, KILLER and TNFRSF10B). DR4 and DR5 are single-pass type I membrane proteins that contain intracellular death domains (DD) and upon activation mediate apoptotic signals (PMID: 11163110). Binding of TRAIL to DR4 or DR5 results in receptor oligomerization and recruitment of FAS-associated protein with death domain (FADD) and caspase 8 to form a functional death-inducing signalling complex (DISC). Upon DISC formation, caspase 8 is cleaved and activated, which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis (PMID: 18813321). DR4 or DR5 promotes the activation of NF-kappa-B and play an important role in inflammation (PMID: 9430227, 19434100).