Mesothelin, also known as CAK1 and ERC, is derived from a 70 kDa precursor that also includes Megakaryocyte Potentiating Factor (MPF) (1-3). The 70 kDa precursor is expressed on the cell surface where it is cleaved at a dibasic proteolytic site to release the 32 kDa glycosylated MPF (3, 4). MPF is a cytokine that potentiates IL-3 induced megakaryocyte colony formation (2, 5). The term Mesothelin refers to the 40 kDa glycosylated protein which remains attached to the cell surface via a GPI linkage. Mesothelin is normally expressed on mesothelial cells in the pleura, pericardium, and peritoneum as well as in the developing and postnatal pancreas (1, 6). It is up-regulated in mesotheliomas and a range of carcinomas and adenomas (7-10). Mesothelin promotes tumor cell proliferation, migration, anchorage-independent growth, and tumor progression, in part through the up-regulation of MMP-7 (9, 11, 12). It is co-expressed with the tumor antigen CA125/MUC16 on advanced ovarian adenocarcinomas and interacts with this molecule to support cell adhesion (13). A soluble form of Mesothelin, with its GPI anchor intact, is released from tumor cells and binds to MMR/CD206 on macrophages (10, 14-16).