HFE (homeostatic iron regulator) is an MHC class I-like protein encoded on chromosome 6 that plays a central regulatory role in iron homeostasis 1. The protein functions by binding to transferrin receptor and modulating hepcidin expression, the primary controller of iron metabolism, thereby regulating intestinal iron absorption 1. Loss-of-function mutations in HFE lead to hereditary hemochromatosis, the most common genetic iron overload disorder in Northern European populations 2. The C282Y mutation accounts for approximately 90% of hemochromatosis cases in individuals of Western European descent 1. Pathologically, HFE mutations result in uninhibited intestinal iron absorption followed by progressive iron accumulation in organs including the liver, pancreas, pituitary, and heart 2. Clinical manifestations vary substantially due to incomplete penetrance, with only 30% of male C282Y homozygotes developing overt disease symptoms such as fatigue, arthralgia, cardiac dysfunction, diabetes, and cirrhosis 3. Early detection is challenging because most patients remain asymptomatic during the preclinical phase 2. Treatment through phlebotomy effectively reduces iron burden and improves outcomes in early-stage disease 2. While HFE mutations account for the majority of hereditary hemochromatosis cases, rarer non-HFE genes (transferrin receptor 2, hemojuvelin, hepcidin) cause phenotypically similar but sometimes more severe forms of iron overload 4.