S100A8 and S100A9, also known as MRP8 and MRP14, are Ca2+-binding proteins that form a heterodimer in neutrophils and monocytes. They play crucial roles in inflammation by modulating leukocyte recruitment, cytokine secretion, and antimicrobial activity. S100A8/A9 is a valuable biomarker for diagnosing and monitoring inflammation-associated diseases, and its blockade using small-molecule inhibitors or antibodies has shown therapeutic potential in animal models. The proteins exhibit dual functions in intracellular and extracellular environments, contributing to both defensive and inflammatory responses. Infection-induced inflammation, metabolic inflammation, and immune system dysfunction all involve the upregulation of S100A8/A9, which can lead to excessive inflammation and tissue damage. Additionally, S100A8/A9 is involved in the progression of degenerative diseases such as osteoarthritis and Alzheimer's disease. The complex has antimicrobial properties and can modulate cellular proliferation, differentiation, and apoptosis. As a result, S100A8/A9 is a promising therapeutic target for various inflammatory and autoimmune diseases. However, more research is needed to fully understand its complex biological functions and mechanisms in different inflammatory conditions.S100A8 and S100A9, also known as MRP8 and MRP14, are Ca2+-binding proteins that form a heterodimer in neutrophils and monocytes. They play crucial roles in inflammation by modulating leukocyte recruitment, cytokine secretion, and antimicrobial activity. S100A8/A9 is a valuable biomarker for diagnosing and monitoring inflammation-associated diseases, and its blockade using small-molecule inhibitors or antibodies has shown therapeutic potential in animal models. The proteins exhibit dual functions in intracellular and extracellular environments, contributing to both defensive and inflammatory responses. Infection-induced inflammation, metabolic inflammation, and immune system dysfunction all involve the upregulation of S100A8/A9, which can lead to excessive inflammation and tissue damage. Additionally, S100A8/A9 is involved in the progression of degenerative diseases such as osteoarthritis and Alzheimer's disease. The complex has antimicrobial properties and can modulate cellular proliferation, differentiation, and apoptosis. As a result, S100A8/A9 is a promising therapeutic target for various inflammatory and autoimmune diseases. However, more research is needed to fully understand its complex biological functions and mechanisms in different inflammatory conditions.