Blvra, known as biliverdin reductase A, is a pleiotropic enzyme that converts biliverdin-IX-alpha into the antioxidant and anti-nitrosative compound, bilirubin-IX-alpha [3]. It is involved in heme degradation and is related to the cellular redox cycle [4]. It may also be associated with pathways like Wnt/β-catenin, as indicated by its role in cancer-related processes [2,3].

In cancer research, knockdown of Blvra in hepatocellular carcinoma (HCC) cell lines (HepG2 and Hep3B) led to reduced cell proliferation, cell cycle progression, invasion, and migration, along with induced apoptosis. It also blocked the activation of the Wnt/β-catenin pathway [2]. In colorectal cancer, overexpression of Blvra increased cell proliferation, migration, invasion, enhanced epithelial-mesenchymal transition (EMT), and hindered apoptosis, with these effects mediated by the Wnt/β-catenin signaling pathway, while knockdown had opposite effects [3]. In a study on oxidative stress-related neurodegeneration, a GK2-Blvra fusion protein protected dopaminergic neuronal cells from oxidative stress in vitro and in vivo in a Parkinson's disease (PD) animal model [1].

In conclusion, Blvra plays diverse roles in biological processes. In cancer, it can promote malignant properties through the Wnt/β-catenin pathway, and its knockdown may have potential anti-cancer effects. In PD, its antioxidant properties can protect dopaminergic neurons. These findings from in vitro and in vivo studies highlight the importance of Blvra in understanding disease mechanisms and developing potential therapeutic strategies.