The mammalian homologs of the CED-4 proteins, Apaf-1 (CED-4), NOD1 (CARD4) and NOD2, contain a caspase recruitment domain (CARD) and a putative nucleotide binding domain, signified by a consensus Walker’s A box (P-loop) and B box (Mg2+-binding site). NOD1 contains a putative regulatory domain and multiple leucine-rich repeats. NOD1 is a member of a growing family of intracellular proteins which share structural homology to the apoptosis regulator Apaf-1. NOD1 associates with the CARD-containing kinase RICK and activates NFkB. The self-association of NOD1 mediates proximity of RICK and the interaction of RICK with IKKg. In addition, NOD1 binds to multiple caspases with long prodomains, but specifically activates caspase-9 and promotes caspase-9-induced apoptosis. NOD2 is composed of two N-terminal CARDs, a nucleotide-binding domain and multiple C-terminal leucine-rich repeats. The expression of NOD2 is highly restricted to monocytes, and activates NFkB in response to bacterial lipopoly-saccharides.