FcRn

FcRn, or neonatal Fc receptor, is an MHC class I–related receptor that binds immunoglobulin G (IgG) and albumin to regulate their half-lives in circulation. Although named for its role in transferring maternal IgG in the neonatal gut, FcRn functions throughout life to protect IgG and albumin from lysosomal degradation and to mediate selective transport of IgG across cellular barriers.

The receptor is a heterodimer consisting of a non-covalently associated heavy chain encoded by the FCGRT gene and the light chain beta-2 microglobulin (B2M). The heavy chain resembles MHC class I molecules and contains α1, α2, and α3 domains. FcRn binds IgG and albumin in a pH-dependent manner, binding strongly in acidic endosomal compartments and releasing their ligands at the cell surface.

In endothelial, placental, renal, and intestinal cells, FcRn takes up IgG and albumin from the bloodstream or lumen, protects them from lysosomal degradation, and recycles or transcytoses them back to the surface, releasing them at neutral pH. This recycling underpins the long serum half-lives of IgG and albumin and influences systemic IgG distribution and immune surveillance.

FcRn is expressed in a variety of tissues, including vascular endothelium, the placenta, the kidneys, and the intestinal epithelium, reflecting its roles in neonatal immunity, maternal-fetal transfer, and homeostatic maintenance of IgG and albumin.

Therapeutically, FcRn is a target for treatments aiming to lower pathogenic IgG levels in autoimmune diseases, with several FcRn inhibitors in development or clinical use. In addition, FcRn contributes to the pharmacokinetics of therapeutic antibodies and albumin-based drugs by modulating their distribution and half-life.