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The pro-inflammatory cytokine IL-1 induces cellular response through two subunits of its receptor, IL-1 receptor I (IL-1RI) and IL-1 receptor accessory protein (IL-1RAcP). IL-1 receptor-associated kinase (IRAK) mediates activation of NF-kappaB, which is a pivotal transcription factor mediating inflammatory and immune response. A novel member in the IRAK/Pelle family has been identified and designated IRAK2. Both IRAK and IRAK2 recruit to the subunits of the IL-1R complex after IL-1 binding and lead to NF-kappaB activation. IRAKs also associate with Toll like receptor (TLR) and the dominant negative mutants of IRAKs inhibit LPS-induced NF-?B activation. Members in IRAK/Pelle family play a central role in IL-1R and TLR mediated inflammatory response. Unlike human IRAK2, murine IRAK2 exists as four alternately spliced isoforms (IRAK2a-d), with two isoforms (IRAK2c and d) acting in an inhibitory fashion. IRAK2 is expressed in a variety of tissues.