The neonatal Fc receptor (FcRn) is an MHC class I–related receptor that plays a central role in the regulation of immunoglobulin G (IgG) and albumin homeostasis. Initially identified for its function in mediating the transfer of maternal IgG to the fetus and newborn, FcRn is now recognized as being broadly expressed in vascular endothelial cells and in most epithelial cell types. In addition, FcRn is widely present in hematopoietic cells, including monocytes, macrophages, dendritic cells (DCs), neutrophils, and B cells (1). Notably, however, the expression pattern of FcRn differs between mice and humans (2,3).
FcRn binds IgG and albumin within acidic endosomal compartments, thereby protecting both molecules from lysosomal degradation and recycling them back to the circulation (4). As a result, the serum half-life of antibodies is directly dependent on FcRn function (5). Beyond its role in maintaining antibody levels, FcRn also contributes to immune surveillance, antigen presentation, and mucosal immunity (1).
Because of its pivotal role in IgG recycling, FcRn has emerged as an important therapeutic target in autoimmune diseases, where FcRn inhibitors are used to lower pathogenic IgG antibody levels (6). Conversely, FcRn-mediated recycling is also harnessed to prolong the serum half-life of therapeutic antibodies and Fc-fusion proteins (7).
