MSRB3 is a methionine sulfoxide reductase that catalyzes the stereospecific reduction of methionine sulfoxide to methionine, functioning as a critical antioxidant enzyme in multiple cellular compartments 1. The protein localizes to the endoplasmic reticulum via an N-terminal signal sequence and contains redox-active cysteines that shuttle oxidizing equivalents during catalysis, coupling MSRB3 activity to dithiol-disulfide exchange reactions in the secretory pathway 1. MSRB3 protects cells from oxidative damage by reducing intracellular reactive oxygen species and maintaining actin redox dynamics 23. Loss of MSRB3 function causes autosomal recessive prelingual deafness (DFNB74), involving profound hearing loss accompanied by stereocilia bundle abnormalities, cuticular plate degeneration, and hair cell apoptosis 24. The disease-causing mechanism involves compromised actin repolymerization capability, as pathogenic variants like p.Cys89Gly cannot repolymerize oxidized actin, leading to altered actin redox ratios in inner ear sensory cells 2. Beyond auditory function, MSRB3 modulates mitochondrial oxidative phosphorylation and protects cardiomyocytes from hypoxia-induced ferroptosis 3, while also regulating endoplasmic reticulum stress-dependent apoptosis in cancer cells 5. These findings establish MSRB3 as essential for maintaining redox homeostasis in specialized sensory and metabolically active tissues.