Insulin Receptor (INSR, CD220) is a type I transmembrane glycoprotein in the Insulin/IGF Receptor family of receptor tyrosine kinases. The mature receptor contains an extracellular alpha subunit and an extracellular/transmembrane/cytoplasmic beta subunit. Alternative splicing generates A and B isoforms which may homodimerize or heterodimerize with the IGF-I receptor. All receptor combinations bind Insulin, IGF-I, or IGF-II, but with differing affinities. Insulin R signaling regulates glucose uptake and metabolism but also contributes to cell growth, differentiation and apoptosis. Mutations in INSR have been linked to severe insulin resistance (type A and Rabson-Mendenhall syndrome), type II diabetes mellitus, and leprechaunism (Donohue syndrome).