S100A2 is a calcium-binding protein belonging to the EF-hand family that functions as both a calcium sensor and signaling modulator 1. It exhibits calcium-dependent protein binding and interacts with diverse cellular molecules, including transcription factors like HNF1A 2. S100A2 is expressed in multiple tissues including mammary epithelium, lungs, kidneys, and prostate glands 1. Mechanistically, S100A2 regulates cellular processes through protein-protein interactions and transcriptional regulation. In clear cell renal carcinoma, S100A2 promotes tumor metastasis by activating GLUT2 transcription via HNF1A interaction, enhancing glucose uptake and glycolytic metabolism 2. In breast cancer, S100A2 characterizes intermediate epithelial-mesenchymal plasticity states associated with metastatic progression 3. S100A2 serves as a biomarker in pancreatic adenosquamous carcinoma 4 and is a marker of basal-like transcriptional subtypes in pancreatic ductal adenocarcinoma 5. S100A2 exhibits dual and context-dependent roles in cancer: while functioning as a tumor suppressor in some contexts 1, it promotes malignancy in others, particularly in renal and breast cancers 23. In non-small cell lung cancer, nuclear S100A2 positivity correlates with improved disease-free survival, suggesting prognostic value 6. S100A2 also associates with inflammatory monocyte activation in rheumatoid arthritis pathogenesis 7 and is identified as a degeneration biomarker in intervertebral disc disease 8.