IRAK2 (interleukin 1 receptor associated kinase 2) is a key signaling adaptor protein that functions downstream of Toll-like receptors and IL-1 receptors to mediate inflammatory responses. The protein promotes NF-κB and MAPK signaling activation through its incorporation into the Myddosome complex alongside MyD88, IRAK4, and other components 1. IRAK2 demonstrates tissue-specific functions, particularly in keratinocytes where it amplifies inflammatory responses by linking proinflammatory signaling with differentiation pathways through the transcription factor ZNF750 2. In cancer contexts, IRAK2 exhibits oncogenic properties by promoting glycolysis-dependent tumor growth through NF-κB activation in pancreatic cancer 3 and supporting aggressive growth in triple-negative breast cancer stem cells 4. The gene undergoes complex regulation, with PELI1-mediated K63 ubiquitination leading to IRAK2 degradation and reduced inflammatory responses in asthma models 5. Notably, murine IRAK2 produces four alternatively spliced isoforms with opposing functions - some promoting and others inhibiting NF-κB activation, providing a negative feedback mechanism for TLR signaling regulation 6. Clinically, IRAK2 serves as a predictive biomarker for radiotherapy response in oral cancer patients 7.