Tumor necrosis factor-related apoptosis-inducing ligand or Apo 2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) family. This group of apoptosis induction pathways all work through protein interactions mediated by the intracellular death domain (DD), encoded within the cytoplasmic domain of the receptor. TRAIL selectively induces apoptosis through its interaction with the Fas-associated death domain protein (FADD) and caspase-8/10 (Wang S & el-Deiry WS 2003; Sprick MR et al. 2002). TRAIL and its receptors, TRAIL-R1 and TRAIL-R2, were shown to be rapidly endocytosed via clathrin-dependent and -independent manner in human Burkitt's lymphoma B cells (BJAB) (Kohlhaas SL et al. 2007). However, FADD and caspase-8 were able to bind TRAIL-R1/R2 in TRAIL-stimulated BJAB cells at 4oC (at which membrane trafficking is inhibited), suggesting that the endocytosis was not required for an assembly of the functional TRAIL DISC complex. Moreover, blocking of clathrin-dependent endocytosis did not interfere with the capacity of TRAIL to promote apoptosis (Kohlhaas SL et al. 2007).