GLRX2 is a mitochondrial glutathione-dependent oxidoreductase that catalyzes the removal of glutathione modifications from proteins, maintaining mitochondrial redox homeostasis 1. The enzyme exhibits high affinity for protein glutathione-mixed disulfides and can facilitate both monothiol and dithiol reactions, efficiently regulating glutathionylation and deglutathionylation of mitochondrial complex I to control superoxide production [UniProt]. GLRX2 loss-of-function protects against metabolic dysfunction through enhanced mitochondrial redox buffering; deletion of Glrx2 in male mice mitigates non-alcoholic fatty liver disease development by reducing hepatic mitochondrial hydrogen peroxide production and protein glutathione mixed disulfides 23. Conversely, GLRX2 is essential for acute myeloid leukemia (AML) cell survival through regulation of the mitochondrial permeability transition pore via ATP5PO glutathionylation; GLRX2 depletion selectively kills primary AML cells while sparing normal hematopoietic cells 1. GLRX2 has been identified as a causal risk factor for polycystic ovary syndrome and is associated with immune dysfunction and metabolic dysregulation 4. The GLRX2 C>T polymorphism (rs912071) impacts urothelial bladder cancer recurrence risk, with the TT genotype associated with increased oxidative stress and recurrence 5. Additionally, GLRX2 regulates bioavailable testosterone through SHBG-mediated mechanisms, with potential implications for testosterone-related metabolic disorders 6.