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Innate immune signaling plays an important role in inflammation, and dysregulation of signaling components within this pathway has been focused as a critical mediator in initiation, progression of inflammatory autoimmune diseases. Toll-like receptors (TLRs) are the most upstream pattern recognition receptors in the immune cells, detecting pathogen associated molecular patterns, initiating signal transduction, by which interleukin-1 receptor-associated kinase (IRAK) family mediates activating signal from TLRs and interleukin-1 receptor. The family comprises of four members, IRAK1, IRAK2, IRAK-M, IRAK4. The family members have a role in either positive or negative regulation of innate immunity, adaptive immunity and inflammation. Accumulated evidence proves that IRAK performs significantly in the pathogenesis of inflammatory autoimmune disorders. On the one hand, both patients and animal modes reported abnormal expression of the family members. On the other hand, functional study in vivo and in vitro demonstrated that the members are implicated in the development of the diseases. Interestingly, IRAK inhibition has potential therapeutic benefits. In this review, we focus on the family, review the physiological roles in different immune cells, and summarize emerging data for highlighting the importance of them in inflammatory autoimmunity. • IRAK family regulates immune cells differentiation, function. • Immune cells play important roles in inflammatory autoimmune diseases. • IRAK family performs significantly in the disorders by these cells. [ABSTRACT FROM AUTHOR]