The myeloid differentiation protein MyD88 was originally characterized as a protein upregulated in myeloleukemic cells following IL-6-induced growth arrest and terminal differentiation. MyD88 is now known to function as an adaptor protein for the association of IRAK with the IL-1 receptor. MyD88 is functionally homologous to the adaptor protein tube in the Toll signaling pathway of Drosophilia, and both proteins are members of the Toll/IL-1R superfamily. MyD88 contains a characteristic N-terminal death domain that is essential for NFkB activation and an adjacent Toll/IL-1R homology domain (TIR domain). Collectively, these domains enable the protein-protein interactions of MyD88 with IRAK and the IL-1 receptor complex.