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The p75 neurotrophin receptor (p75NTR) is a member of the tumor necrosis receptor superfamily and can mediate cell death and cell survival in response to nerve growth factor (NGF) (1 for review). The p75NTR-associated cell death executor (NADE) mediates apoptosis by interacting with the cell death domain of p75NTR following the binding of NGF by p75NTR.2 Recent studies have shown that NADE also interacts with second mitochondria-derived activator of caspase (Smac). Co-expression of NADE and Smac promotes TRAIL-induced apoptosis and inhibits XIAP-mediated Smac ubiquitization. It has been suggested that it is this interaction between NADE and Smac that allows apoptosis to proceed. Finally, although initially discovered as an mRNA expressed in ovarian granulosa cells,3 NADE has been suggested to play a role in the neuronal death seen in epileptic brain damage.4