S100A12 is a calcium-binding protein that functions as a key regulator of inflammatory processes and immune responses. The protein is primarily expressed by neutrophils and monocytes/macrophages and acts as an alarmin or danger-associated molecular pattern (DAMP) molecule 1. S100A12 exerts its pro-inflammatory effects by binding to the receptor for advanced glycation end-products (RAGE), which activates NF-κB and MAP-kinase signaling pathways, leading to cytokine production and upregulation of adhesion molecules 2. The protein demonstrates antimicrobial activity through nutritional immunity, chelating essential metal nutrients from pathogens to inhibit their growth 1. S100A12 also promotes neutrophil extracellular trap (NET) formation through interaction with Annexin A5, enhancing calcium influx and contributing to inflammatory tissue damage 3. Clinically, S100A12 serves as a valuable biomarker for disease severity and prognosis across multiple conditions. Elevated S100A12 levels correlate with poor outcomes in idiopathic pulmonary fibrosis, predicting mortality and disease progression 4. The protein also shows promise as a cardiovascular biomarker, with serum levels predicting future cardiovascular events and correlating with atherosclerosis progression 5. Additionally, S100A12 has emerged as a biomarker in autoimmune diseases, where its dysregulation is associated with disease activity and therapeutic response monitoring 6.