ST2 is a member of the interleukin-1 receptor family and it is also known as interleukin-1 receptorlike 1 (IL1RL-1). ST2 exists in two isoforms: a transmembrane or cellular (ST2L) and soluble or circulating (sST2). ST2 is the receptor for interleu-kin-33 (IL-33), which is an IL-1-like cytokine that is secreted by living cells in response to cell damage. The IL-33 exerts its effects by binding to the transmembrane receptor ST2L isoform. The interaction of IL-33 and ST2L has been shown to be cardioprotective, reducing myocardial fibrosis, cardiomyocyte hypertrophy, apoptosis, and improving myocardial function. The IL-33/ST2 system is upregulated in cardiomyocytes and fibroblasts in response to cardiac injury. sST2 avidly binds to IL-33 and competes with ST2L. The interaction of the soluble ST2 with IL-33 blocks the IL-33/ST2L system and as a result eliminates the cardioprotective pathway of the IL-33/ST2L interaction. ST2L contains an extracellular domain of three immunoglobulin-like motifs, a transmembrane segment, and an intracellular cytoplasmic domain, whereas sST2 lacks the transmembrane and cytoplasmic domains. Three linked immunoglobulinlike motifs of sST2 have a total length of 310 amino acid residues. The expression of sST2 is largely inducible and it is almost ubiquitous in living cells, such as resting fibroblasts. It has been suggested that sST2 is produced by both cardiac fibroblasts and cardiomyocytes in response to cardiac injury or cardiac stress, macrovascular (aortic and coronary artery), and heart microvascular endothelial cells in response to diastolic load.