IGF-II (Insulin-like growth factor II; also multiplication-stimulating polypeptide/MSP and somatomedin-A) belongs to the insulin family of peptide growth factors. It is part of a complex system of growth and metabolic-regulating proteins that is particularly important during development. It has been associated with nervous system proliferation and differentiation, myelination, adrenal cortical proliferation, and skeletal growth and differentiation. In human, IGF-II is primarily synthesized by the liver, and circulates at high levels in both fetus and adult. In rodent, however, IGF-II levels drop after the perinatal period. IGF-II is produced by astrocytes, hepatocytes, osteoblasts, embryonic striated muscle cells plus Kupffer cells and Ito cells. IGF-II binds to IGF-I R, Insulin R (IR)-type A, IGF-I R:Insulin R-A hybrids, IGF-II R, and IGF binding proteins 1-6. The first three receptors initiate downstream signaling events, the IGF-II R sequesters local IGF-II, and the six IGFBPs regulate IGF-II activity in various tissues.