CYBRD1 encodes duodenal cytochrome b (Dcytb), a plasma membrane ferric reductase essential for dietary iron absorption 1. The protein functions as a transmembrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) to Fe(2+), the transportable form of iron required for uptake by duodenal enterocytes 1. Structurally, CYBRD1 contains two heme groups per monomer with four conserved histidine residues serving as heme ligands, and exhibits redox properties with a midpoint potential of +80 mV 1. The protein can be reduced by ascorbate under anaerobic conditions and shows EPR signals consistent with bis-histidine coordination typical of the cytochrome b561 family 1. CYBRD1 expression is dysregulated in hereditary hemochromatosis, where inappropriate regulatory cues contribute to excessive duodenal iron absorption 2. Genetic variants in CYBRD1, particularly rs884409, act as phenotypic modifiers in HFE-related hemochromatosis, influencing serum ferritin levels and transferrin saturation 3. Beyond iron metabolism, CYBRD1 has been implicated in cancer biology, with altered expression associated with colorectal cancer metastasis, mesothelioma risk, and serving as a prognostic biomarker in ovarian cancer 456.