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Death effector domains (DEDs) are protein-protein interaction structures that are found in proteins that regulate a variety of signal transduction pathways. DEDs are a part of the larger family of Death Domain structures that have been primarily described in the control of programmed cell death. The seven standard DED-containing proteins are fas associated death domain protein (FADD), Caspase-8 and 10, cellular FLICE-like inhibitory protein (c-FLIP), death effector domain containing DNA binding (DEDD), DEDD2 and phosphoprotein enriched in astrocytes 15-Kda (PEA-15). These proteins are particularly associated with the regulation of apoptosis and proliferation mediated by the tumor necrosis factor alpha (TNFalpha) receptor family. Consequently DED-containing proteins are reported to regulate transcription, migration, and proliferation, in addition to both pro and anti-apoptotic functions. Moreover, DED proteins are essential in embryonic development and homeostasis of the immune system. Here we focus on the role of DED-containing proteins in development and the pathologies arising from abnormal expression of these proteins.