IRAK2

IRAK2 (interleukin-1 receptor-associated kinase 2) is a central component of innate immune signaling downstream of interleukin-1 receptors (IL-1Rs) and most Toll-like receptors (TLRs), where it functions within the MyD88-dependent myddosome complex to regulate inflammatory gene expression and host defense responses^[1][2]. Mechanistically, IRAK2 promotes TRAF6 ubiquitination and subsequent activation of NF-κB and MAPK signaling pathways, thereby sustaining transcriptional programs that drive cytokine production during innate immune activation^[3][4]. Unlike the transient activity of IRAK1 during early TLR signaling, IRAK2 is particularly important for maintaining late-phase TLR-dependent responses and prolonged inflammatory gene expression, highlighting a nonredundant role within the IRAK family^[4]. IRAK2 also contributes to post-transcriptional regulation of inflammatory mediators, and genetic deletion impairs the production of multiple inflammatory transcripts, further supporting its function as a regulator of sustained immune responses^[5]. In disease contexts, dysregulated IRAK2 signaling has been associated with inflammatory disorders, altered susceptibility to infection, and multiple cancer types in which IRAK2 expression correlates with immune-related pathways and tumor progression^[1][2]. Compared with related isoforms, murine Irak2 undergoes alternative splicing to generate four isoforms, including the stimulatory Irak2a and Irak2b variants and the inhibitory Irak2c and Irak2d variants, demonstrating isoform-specific regulation of NF-κB signaling and negative-feedback control of TLR responses^[6]. Therefore, IRAK2 serves as an important experimental target for investigating innate immunity, inflammatory signaling, and immune-associated disease mechanisms^[1][2][5].