Suppression of Tumorigenicity 2 (ST2), also known as IL-1 R4, is an Interleukin-1 receptor family glycoprotein that contributes to Th2 immune responses. ST2 is expressed on the surface of mast cells, activated Th2 cells, macrophages, and cardiac myocytes. ST2 binds IL-33, a pro-inflammatory IL-1 family cytokine with intracellular and extracellular activities. In addition to its role in promoting mast cell and Th2 dependent inflammation, transmembrane ST2 activation enhances inflammation-associated hypernociception and protects from atherosclerosis and cardiac myocyte hypertrophy. The soluble ST2 isoform is elevated in the serum under inflammatory conditions including allergic asthma, sepsis, trauma, dengue fever, and pulmonary disease. Serum ST2 elevation is also associated with multiple aspects of heart failure including aortic stenosis, congestive cardiomyopathy, and risk of cardiovascular heart failure and death.