Juvenile hemochromatosis is an early-onset autosomal recessive disorder characterized by iron overload, leading to cardiomyopathy, diabetes, and hypogonadism. This condition is linked to the centromeric region of chromosome 1q, which is incomplete in the human genome assembly. The study reports the positional cloning of the locus associated with juvenile hemochromatosis and identifies a new gene crucial to iron metabolism, named HFE2, also known as hemojuvelin. The gene is expressed in liver, heart, and skeletal muscle, similar to hepcidin, a key protein in iron metabolism. Analysis of multiple families from different populations revealed a common mutation, G320V, which accounts for two-thirds of the mutations found. Hemojuvelin is predicted to be a membrane-bound receptor or secreted polypeptide hormone, and its expression is modulated by hepcidin. The study suggests that hemojuvelin may play a role in regulating hepcidin levels, which are depressed in individuals with juvenile hemochromatosis. This discovery opens new therapeutic and diagnostic opportunities for managing iron-related disorders.Juvenile hemochromatosis is an early-onset autosomal recessive disorder characterized by iron overload, leading to cardiomyopathy, diabetes, and hypogonadism. This condition is linked to the centromeric region of chromosome 1q, which is incomplete in the human genome assembly. The study reports the positional cloning of the locus associated with juvenile hemochromatosis and identifies a new gene crucial to iron metabolism, named HFE2, also known as hemojuvelin. The gene is expressed in liver, heart, and skeletal muscle, similar to hepcidin, a key protein in iron metabolism. Analysis of multiple families from different populations revealed a common mutation, G320V, which accounts for two-thirds of the mutations found. Hemojuvelin is predicted to be a membrane-bound receptor or secreted polypeptide hormone, and its expression is modulated by hepcidin. The study suggests that hemojuvelin may play a role in regulating hepcidin levels, which are depressed in individuals with juvenile hemochromatosis. This discovery opens new therapeutic and diagnostic opportunities for managing iron-related disorders.