Maintaining or improving muscle function, in aging or disease patients, has significant potential to improve the quality of life. In fact, optimal metabolic functioning of skeletal muscle, which makes up 30-40% of an adult’s body mass, is one of the best predictors of overall health. To identify potential regulators of skeletal muscle metabolism and function, we performed a proteomic analysis of gastrocnemius muscle from 73 genetically distinct inbred mouse strains and integrated the data with genomics and >300 molecular/phenotypic traits via quantitative trait loci (QTL) mapping and correlation network analysis. These data identified thousands of associations between skeletal muscle protein abundance and molecular/phenotypic traits, including plasma metabolites, lipids and cytokines; whole body measurements such as glucose/insulin sensitivity and body composition/organ weights; and muscle phenotypes such as cardiac and skeletal muscle function such as grip strength. We created an interactive web resource to explore the data at http://muscle.coffeeprot.com/. We next used this resource to target 27 genes focusing on negative associations to muscle function and performed a functional genomic screen in human micro-muscles. This screen incorporated high-throughput assessment of contractile force production and identified a series of negative regulators of muscle function including UFC1, an E2 ligase for protein UFMylation. We show that UFMylation is up-regulated in a mouse Amyotrophic Lateral Sclerosis (ALS) model of muscle atrophy. Furthermore, in vivo knockdown of UFMylation increased ex vivo muscle function via enhanced synthesis of ribosomal and contractile proteins, and decreased protein degradation pathways including K48-linked ubiquitination. These data provide a resource to identify regulators of muscle metabolic function.