IGF-I R/IGF1R (Insulin-like Growth Factor I Receptor), also known as CD221, is a ubiquitously expressed heterotetrameric transmembrane glycoprotein consisting of two alpha and two beta subunits. It binds IGF-1 with high affinity, IGF2 with lower affinity, and Insulin with lowest affinity. IGF1R/Insulin R hybrids respond primarily to IGF-1 and may downregulate cellular responses to Insulin. IGF signaling is also modulated by IGF binding proteins and the scavenger receptor, IGF-II R/IGF2R. Mice lacking IGF1R show intrauterine growth deficiency and die at birth due to respiratory failure, and IGF1R mutations in humans can retarded pre- and postnatal growth. IGF-1 and its receptor are particularly important for neurogenesis, with deficiency producing microcephaly and learning disorders. IGF1R expression on human embryonic stem cells is important for their survival and clonogenicity.