Insulin-like growth factors (IGFs) comprise a family of endocrine, paracrine and autocrine polypeptides consisting of the ligands IGF1 and IGF2, two receptors (IGF1R, IGF2R), at least 6 IGF-binding proteins (IGFBPs) and IGFBP proteases. Among the binding proteins, IGFBP6 is unique because of its N-terminal disulfide linkages and its marked binding preference for IGF2. It is a potent inhibitor of the interaction between IGF2 and its receptor IGF1R, thus preventing major functions of IGF2, such as induction of proliferation, differentiation, cell adhesion, or colony formation. In particular, IGFBP-6 inhibited the growth of neuroblastoma and rhabdomyosarcoma xenografts. GFBP-6 is expressed in many tissues, including lung, liver, gut and the central nervous system.