Beta-2-Microglobulin (b2M)

β2 microglobulin lies lateral to the α3 chain on the cell surface. Unlike α3, β2 has no transmembrane region. Directly above β2 lies the α1 chain, which itself is lateral to the α2. β2 microglobulin associates not only with the alpha chain of MHC class I molecules, but also with class I-like molecules such as CD1 and Qa.

An additional function is association with the HFE protein, together regulating the expression of hepcidin in the liver which targets the iron transporter ferroportin on the cytoplasmic membrane of enterocytes and macrophages for degradation resulting in decreased iron uptake from food and iron release from recycled red blood cells respectively. Loss of this function causes iron excess and hemochromatosis.