BLVRA (biliverdin reductase A) catalyzes the reduction of biliverdin IXα to bilirubin, the final step in heme catabolism 1234. The enzyme uses NADH or NADPH as cofactors depending on pH conditions, with NADPH being the likely physiological substrate 234. Beyond its canonical metabolic role, BLVRA exhibits antioxidant and cytoprotective properties relevant to neurodegeneration and cancer. A GK2-BLVRA fusion protein protected dopaminergic neurons from oxidative stress in Parkinson's disease models through ROS reduction and apoptosis suppression 5. In glioblastoma, BLVRA promotes tumor progression by regulating fatty acid metabolism; BLVRA knockdown suppressed cell proliferation, disrupted lipid homeostasis, and induced apoptosis 6. Clinically, BLVRA genetic variants significantly influence neonatal hyperbilirubinemia susceptibility in Chinese populations. The rs699512 G-allele confers protective effects (OR=0.84) 7, while other variants show disease associations 89. Additionally, elevated bilirubin produced via BLVRA activity associates with cardiovascular protection 1011. These findings establish BLVRA as a metabolic enzyme with dual roles in heme catabolism and diverse pathophysiological processes.