Hfe, also known as human homeostatic iron regulator, is a gene encoding an MHC class I-like protein that binds beta-2 microglobulin. It influences iron absorption by modulating the expression of hepcidin, the main controller of iron metabolism, thus playing a crucial role in iron homeostasis [3].

Primary Type 1 or HFE hemochromatosis results from homozygous mutations in the Hfe gene, accounting for approximately 90% of all hemochromatosis cases. Non-HFE hemochromatosis types, which do not involve the Hfe gene, are extremely rare [1]. Mouse models have consistently demonstrated robust neuroprotection against toxins known to increase the risk of neurodegenerative disease in relation to Hfe variants, suggesting an adaptive or hormetic response to increased iron [2].

In conclusion, Hfe is essential for iron homeostasis. Model-based research, especially from mouse models, has revealed its role in diseases such as hemochromatosis and neurodegenerative disorders. Understanding Hfe's function provides insights into the mechanisms of iron-related diseases and may offer potential directions for treatment.

References:

1. Turshudzhyan, Alla, Wu, David C, Wu, George Y. 2023. Primary Non-HFE Hemochromatosis: A Review. In Journal of clinical and translational hepatology, 11, 925-931. doi:10.14218/JCTH.2022.00373. https://pubmed.ncbi.nlm.nih.gov/37408807/

2. Marshall Moscon, Savannah L, Connor, James R. 2024. HFE Mutations in Neurodegenerative Disease as a Model of Hormesis. In International journal of molecular sciences, 25, . doi:10.3390/ijms25063334. https://pubmed.ncbi.nlm.nih.gov/38542306/

3. Barton, James C, Edwards, Corwin Q, Acton, Ronald T. 2015. HFE gene: Structure, function, mutations, and associated iron abnormalities. In Gene, 574, 179-92. doi:10.1016/j.gene.2015.10.009. https://pubmed.ncbi.nlm.nih.gov/26456104/