Amphiregulin (AREG) is one of the ligands of the epidermal growth factor receptor (EGFR). AREG plays a central role in mammary gland development and branching morphogenesis in organs and is expressed both in physiological and in cancerous tissues. The AREG protein is synthesized as a 252-amino acid transmembrane precursor, pro-AREG. At the plasma membrane, pro-AREG is subjected to sequential proteolytic cleavages within its ectodomain and is then released as the soluble AREG protein. Depending on the cell type and microenvironment, AREG can be produced in multiple cellular and mature forms using alternative pro-AREG cleavage sites and glycosylation motifs.