HFE also known as HLA-H is a membrane protein that is similar to MHC class I-type proteins and associates with beta2-microglobulin (beta2M). HFE plays a crucial role in iron homeostasis by regulating iron absorption in the intestine, which is vital for preventing iron overload conditions such as hereditary hemochromatosis. This condition can lead to serious health issues, including liver cirrhosis, diabetes, skin hyperpigmentation, and heart failure. HFE is primarily localized in the crypt enterocytes of the duodenum, where HFE interacts with the transferrin receptor, forming a stable complex essential for iron transport. This intracellular localization allows HFE to effectively modulate iron uptake and release, thereby maintaining iron balance in the body.