IGF-II/IGF2 (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, IGF2 is primarily synthesized by the liver, and circulates at high levels in both fetus and adult. In rodent, however, IGF2 levels drop after the perinatal period. IGF2 is produced by astrocytes, hepatocytes, osteoblasts, embryonic striated muscle cells plus Kupffer cells and Ito cells. IGF2 binds to IGF1R, Insulin R (IR)-type A, IGF1R:Insulin R-A hybrids, IGF2R, and IGF binding proteins 1-6. The first three receptors initiate downstream signaling events, the IGF2R sequesters local IGF2, and the six IGFBPs regulate IGF2 activity in various tissues.