BRCA1 is classically known as a tumor suppressor gene that acts to maintain genomic stability in mammary cells. However, BRCA1 mRNA expression is found in a variety of cell types, including skeletal muscle, without a defined physiological role in those cells. The purpose of these studies was to use a translational approach to determine if BRCA1 plays a critical role in the regulation of physiological and metabolic function of skeletal muscle. We found that BRCA1 mRNA and protein is expressed in skeletal muscle biopsies from humans and adult mice. To determine if BRCA1 is critical for skeletal muscle function, we generated inducible skeletal muscle specific BRCA1 knock out mice (BRCA1KOsm). Further, using shRNA approaches we significantly reduced BRCA1 expression in cultured human myotubes (BRCA1sh). Using in vivo and in vitro approaches, our data suggest that induced deletion of BRCA1 expression leads to significant dysfunction of adult skeletal muscle. When compared to age-matched wild-type (WT) mice, BRCA1KOsm develop visible kyphosis and detectable muscle weakness as measured by in situ muscle contractions. In addition, we found reductions in mitochondrial oxygen consumption and alterations in glucose dynamics of BRCA1KOsm and BRCA1sh when compared to the WT mice or control myotubes, respectively. Finally, using immuno-precipitation approaches we have identified that BRCA1 can complex with the phosphorylated form of acetyl CoA-carboxylase. Our data show that loss of BRCA1 specific to skeletal muscle leads to the development of muscle weakness and reductions in mitochondria function. When considering the high degree of susceptibility of BRCA1 to genetic mutation our data suggest that further human genetic association studies are potentially warranted. Collectively, our results suggest the BRCA1 pathway is a novel target that is necessary for optimal function of skeletal muscle.