CYB5R1 (cytochrome b5 reductase 1) is an NADH-cytochrome b5 oxidoreductase that plays dual roles in cellular metabolism and pathological processes. The enzyme catalyzes electron transfer from NADH to cytochrome b5, functioning in fatty acid desaturation, cholesterol biosynthesis, and drug metabolism 1. However, CYB5R1 also promotes ferroptosis, a form of iron-dependent cell death, by transferring electrons from NADH to oxygen, generating hydrogen peroxide that leads to lipid peroxidation of polyunsaturated fatty acid-containing membrane phospholipids 1. This ferroptotic activity disrupts membrane integrity and contributes to cell death 2. Clinically, CYB5R1 expression is associated with epithelial-mesenchymal transition and poor prognosis in colorectal cancer 3. The enzyme serves as a diagnostic biomarker for acute myocardial infarction, where ferroptosis-related mechanisms contribute to cardiac damage 4. Additionally, CYB5R1 is upregulated during 25-hydroxycholesterol-induced ferroptosis and is linked to various immune cell infiltration patterns in cancer 56. The protein is also implicated in polycystic ovary syndrome through its role in steroid metabolism and mitochondrial function 7.