CYB5B (cytochrome b5 type B) is a mitochondrial hemoprotein that functions as an electron carrier for membrane-bound oxygenases 1. As a crucial component of the mitochondrial electron transport system, CYB5B participates in sterol C4-demethylation during cholesterol biosynthesis, where it compensates functionally with its microsomal counterpart CYB5A 1. CYB5B also serves as an essential electron donor in the mARC-containing N-reductase system, catalyzing the reduction of N-hydroxylated compounds in a heme-dependent manner 2. Mechanistically, CYB5B operates within mitochondrial redox pathways and responds to oxidative stress 3. Recent evidence demonstrates that CYB5B expression is regulated by MTCH2 (mitochondrial carrier homolog 2) and modulates mitochondrial membrane potential and permeability transition pore function 4. Additionally, CYB5B is upregulated by unidirectional blood flow in vascular endothelium as part of antioxidant defense mechanisms 3. Clinically, CYB5B dysregulation associates with multiple pathologies: it is overexpressed in Hodgkin lymphoma and aggressive non-Hodgkin lymphomas, potentially serving as an antibody therapy target 5; it plays a protective role in acetaminophen-induced acute liver failure when regulated by miR-375 6; and elevated CYB5B expression correlates with adverse neurodevelopmental outcomes in preterm infants exposed to neonatal stress 7.