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 NF?B. The self-association of Nod1 mediates proximity of RICK and the interaction of RICK with IKK?. In addition, Nod-1 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 NF?B in response to bacterial lipopoly-saccharides.