Cells undergo apoptotic programmed cell death in response to various stimuli, and this key mechanism is necessary for cellular morphogenesis, tissue homeostasis, and host defense. Particular cytokines such as tumor necrosis factor (TNF) and the Fas ligand signal through their cooperative death domain-containing receptors tumor necrosis factor receptor 1 (TNFR1) and Fas. Like its cousin TRAIL-R1, TRAIL-R2 is widely expressed in both normal tissues as well as in many types of tumor cells.