BDH2 is an NAD(H)-dependent oxidoreductase with dual roles in iron metabolism and cellular stress responses. The protein catalyzes synthesis of the mammalian siderophore 2,5-dihydroxybenzoate (2,5-DHBA), which chelates cytoplasmic iron and facilitates its transfer into mitochondria to support heme synthesis and bioenergetics. In melanoma, BDH2 localizes to mitochondria-lysosome contacts where it orchestrates inter-organelle iron redistribution, thereby controlling ferroptosis vulnerability 1. BDH2 also exhibits tumor-suppressive functions across multiple cancer types. In gastric cancer, BDH2 overexpression induces apoptosis and autophagy by promoting Nrf2 ubiquitination, leading to reactive oxygen species accumulation and inhibition of the PI3K/Akt/mTOR pathway 2. Similar Akt/mTOR-mediated apoptosis has been demonstrated in lung adenocarcinoma 3. In colorectal cancer, BDH2 enhances 5-fluorouracil sensitivity through GLIPR1 promoter methylation 4. Clinically, elevated BDH2 expression in myelodysplastic syndrome correlates with increased leukemia transformation risk and shorter leukemia-free survival 5. BDH2 is also implicated in immune regulation; in systemic lupus erythematosus, the miR-21/BDH2 axis drives iron accumulation and promotes pathogenic T follicular helper cell differentiation 6. Hypoxia partially upregulates BDH2 expression in cardiomyocytes, suggesting a role in cardiac stress adaptation 7.