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The MYD88 gene (myeloid differentiation primary response gene 88) at 3p22.2 codes for the 296 amino acid pro-peptide of myeloid differentiation primary response protein MyD88, a key effector of innate immunity. As well as homodimers it forms heterodimers with the TIR domain-containing adapter protein (Toll/interleukin-1 receptor domain-containing adapter protein). There are 6 isoforms.

Myeloid differentiation primary response protein MyD88 is an adapter protein that forms dimers involved in the Toll-like receptor and IL-1 receptor signalling pathway in the innate immune response leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. MyD88 links IL-1 receptor or TLR family members with a C-terminal TIR (Toll IL-1R) domain interaction. The N-terminal death domain (DD) associates with IL-1R-associated kinase (IRAK) family kinases via homotypic protein-protein interaction. A complex is formed called the myddosome made up of a ring of six MyD88 and four IRAK2 DDs in a helix. MyD88-mediated signalling in intestinal epithelium maintains gut homeostasis and controls the expression of the antimicrobial lectin regenerating islet-derived protein 3-gamma.

Defects cause life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. It also protects against endotoxic shock, so the death may not be rapid ! The gene is highly conserved in animals.The MYD88 mutation L265P is very common in Waldenstrom's macroglobulinaemia.

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