Abstract

Albumin is the most abundant protein in blood and fulfills essential roles in distribution and transport of an array of compounds such as nutrients, metabolites, hormones, drugs and toxins. It shares a long serum half-life of three weeks with the IgG class of antibodies. The long half-life has made IgG the preferred choice for antibody-based therapeutics, while albumin is utilized as fusion partner for small protein therapeutics. Surprisingly, a common molecular mechanism extends the half-life of both, as they are rescued from degradation by a single receptor, named the neonatal Fc receptor (FcRn), expressed in endothelial cells lining the blood vessels and hematopoietic cells. Beside its role as a homeostatic regulator, FcRn has also been found to be a versatile receptor with several important functions at different body sites, as for instance transport of IgG across mucosal surfaces and from mother to fetus across placenta, as well as enhancement of antigen presentation and cross-presentation in dendritic cells. Hence, increasing appreciation of the unique roles of FcRn as a multiplayer in immune regulation has triggered intense interest from both academia and biotech companies. Here, I will summarize our current cellular and molecular understanding of FcRn biology and demonstrate how ligand interaction with FcRn can be manipulated for improved therapeutic efficacy.