Myeloid Differentiation Primary Response 88 Protein

Background

MYD88 is a key adaptor protein involved in innate immune signaling downstream of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). It contains a death domain (DD) and a Toll/IL-1 receptor (TIR) domain, enabling interaction with upstream receptors and downstream signaling proteins. Upon activation, MYD88 recruits IRAK kinases (IRAK1/IRAK4) and TRAF6, leading to activation of NF-κB, MAPK, and JNK pathways, which regulate inflammation, cytokine production, and cell survival. MYD88 is essential for host defense against bacterial, viral, and fungal infections. Mutations in MYD88 are associated with immune dysregulation, such as autoimmune diseases and lymphomas, including Waldenström macroglobulinemia. Knockout studies show impaired immune responses, increased susceptibility to infections, and defects in pro-inflammatory cytokine production, underscoring MYD88's central role in innate immunity.