Other functions of Nox4 in skeletal muscle include sensing oxygen tension,18 controlling metabolism,27 oxidizing RyR1 in mouse models of bone metastases of breast cancer,19 and regulating remodeling of dystrophic muscle.33 Critical roles have been demonstrated for Nox4 in the heart that include26 serving as the source of oxidative stress in heart failure.26 The availability of cKO and muscle-specific Cre expression systems should provide powerful tools for further elucidating the roles of Nox4 in normal physiology and disease. This evidence concerns the gene RYR1 and breast carcinoma.