TMEM219 is a recently discovered death receptor, which induces cell apoptosis by a Caspase-8-dependent mechanism, through the binding with its ligand, the Insulin-like growth factors binding protein 3 (IGFBP3). TMEM219 consists of four exons comprising the 915-base pair cDNA sequence on chromosome 16q13 and represents a 240-amino acid polypeptide. TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. TMEM219 is an IL-13Rα2 binding partner that plays a critical role in many Chi3l1-induced, IL-13Rα2-mediated cellular and organ responses.