S100A9 is a calcium- and zinc-binding protein that plays critical roles in inflammatory processes and immune responses, particularly in neutrophil function and tissue repair. The protein undergoes post-translational modifications including lactylation at lysine 26, which promotes neutrophil trafficking and cardiac inflammation in myocardial ischemia/reperfusion injury 1. S100A9 functions as a damage-associated molecular pattern (DAMP) molecule, activating immune responses through TLR4 and RAGE signaling pathways 2. In sepsis, S100A9 contributes to immunosuppression through HLA-DR^low S100A^high monocytes that inhibit CD4+ T cell responses 3. The protein exhibits tissue-specific functions: in myocardial infarction, S100A9 is essential for both inflammatory and reparatory phases, with extended blockade impairing cardiac recovery 4; in cancer, intracellular S100A9 drives brain metastasis through ALDH1A1-retinoic acid signaling 5; and in ischemic stroke, S100A9 deletion in microglia/macrophages promotes neuroprotection via STAT6/PPARγ signaling 6. During neonatal development, S100A9 regulates gut microbiota composition and immune system maturation, with deficiency leading to increased susceptibility to sepsis and altered metabolic outcomes 7. In pancreatitis, S100A9 mediates NLRP3 inflammasome activation through VNN1-dependent ROS release 8.