S100a9, a Ca2+ binding protein, belongs to the S100 family. It is mainly expressed in neutrophils and monocytes and plays crucial roles in modulating inflammatory responses and inflammation-associated diseases. S100a9 often forms a heterodimer with S100a8 (S100A8/A9), participating in multiple signaling pathways like Toll-like receptor 4/MyD88/NF-κB, IL-17-NFκB-caspase-3, and is involved in various biological processes including tumor development, myocardial infarction response, and skin inflammation regulation [1,2,4].

In gene knockout studies, S100a9-KO mice have shown that long-term S100a9 blockade negatively impacts cardiac recovery after myocardial infarction, as it reduces the proliferation of certain hematopoietic stem and progenitor cells and impairs monocyte-macrophage transition [2]. In hepatocellular carcinoma, depletion of S100a9 dampens tumor growth and metastatic ability [3]. In rosacea-like mouse models, inhibition of S100a9 suppresses disease progression and inflammatory responses [4]. In myocardial ischemia-reperfusion mouse models, targeting S100a9 with a specific inhibitor mitigates acute inflammatory damage and fibrosis [5]. In sepsis-induced acute lung injury, S100a9 knockout alleviates lung damage and epithelial cell apoptosis [6]. In sepsis-induced acute liver injury, S100a9-KO mice show attenuated liver dysfunction and injury with improved mitochondrial function [7]. In acute pancreatitis, pancreatic ductal deletion of S100a9 alleviates the injury by inhibiting NLRP3 activation [8].

In conclusion, S100a9 is significantly involved in inflammation, tissue repair, and tumor-related processes. Gene knockout models of S100a9 have revealed its roles in diseases such as myocardial infarction, cancer, rosacea, and various inflammatory diseases, highlighting its potential as a therapeutic target for these conditions.