MyD88, a protein involved in interleukin-1 (IL-1) mediated signalling was originally isolated as myeloid differentiation primary response gene (3,4). MyD88 possesses a N-terminal death domain similar to cytoplasmic segments of TNF receptor 1, Fas, and C-terminal region related to IL-1 and Toll receptors. Overexpression of MyD88 induces activation the c-Jun N-terminal kinase and NF-κ,B through its death domain (1,2). The C-terminus of MyD88 interacts with the IL-1 receptor and blocks NF-κ,B activation induced by IL-1, but not by NF-κ,B. The pro-inflammatory cytokine IL-1 induced cellular response requires IL-1 receptor complex including IL-1RI and IL-1RAcP. Recently, MyD88 was identified as an adapter molecule in the IL-1 signaling pathway. MyD88 associates with and recruits IRAK to the IL-1 receptor complex in response to IL-1 treatment and dominant negative form of MyD88 attenuates IL-1R-mediated NF-κ,B activation. MyD88 is also employed as a regulator molecule by IL-18 receptor and human Toll receptor, which are members in the Toll/IL-1R family of receptors. Targeted disruption of the MyD88 gene results in lose of cellular responses to IL-1 and IL-18, and MyD88-deficient mice lack responses to bacterial product LPS that employs Toll-like receptors 2 and 4 (TLR2 and TLR4) as the signaling receptors. MyD88 is a general adapter protein for the Toll/IL-1R family of receptors and plays an important role in the inflammatory response induced by cytokines IL-1 and IL-18 and endotoxin. MyD88 gene is expressed in many tissues.