The present invention provides nucleic acids and polypeptides for IRAK-4, a novel member of the IRAK family of protein kinases. Members of the IRAK family are indispensable signal transducer for members of the IL-1R/Toll family of transmembrane receptors, including IL-1 receptors, IL-18 receptors and LPS receptors. IRAK-4 sequences from human and mouse are provided, as are methods for identifying compounds useful in the treatment or prevention of inflammatory diseases.