Apoptosis and inflammation are important cellular processes that are highly regulated through specific protein-protein interactions (PPI). Proteins involved in these signaling cascades often carry PPI domains belonging to the death-domain superfamily (reviewed in Kohl A and MG Grutter, 2004). These PPI domains include the death effector domain (DED), the death domain (DD), the caspase activation and recruitment domain (CARD) and the pyrin domain (PYD). PPI domains are structurally related and comprised of a six alpha helical structure; within proteins PPI domains can be found in isolation or in combination with other domains. DEDD2/Flame-3 (DED containing DNA binding2) belongs to a family of single DED-containing proteins that is targeted to the nucleus (reviewed in Barnhart et al, 2003; Slvibst ry sl, 2003). Several DED-containing proteins are involved in the regulation of apoptosis through their interactions with DED-containing caspases. It is thought that DEDD2 and its closely related homologue DEDD may mediate cell death by binding to the DED-containing caspases -8 and -10, and targeting them to the nucleus following death receptor induced apoptosis. However, the function of DEDD2 and DEDD remain to be fully elucidated, and they may also have roles in cellular processes other than apoptosis.