Our results are also in agreement with reports that DR5 (but not DR4) is critical in TRAIL-mediated apoptosis in CRC cells [45], and in concordance with the overall principle that death TNF ligands can function intracellularly, as exemplified (a) by the ability of FasL to signal Fas-mediated apoptosis via the Golgi and/or ER apparatus [46] and (b) by our previous intriguing observations on the ability of intracellular TRAIL to cause extensive toxicity in cells that are normally totally refractory to extracellular TRAIL (discussed in [33]). The gene discussed is TNFRSF10B; the disease is colorectal carcinoma.