DJ-1 is a causative gene for a familial form of Parkinson disease. DJ-1 deficient mice develop progressive behavioral abnormalities in gaits and forearm grip strength are hypoactive. The mechanisms under the activity are not fully known. Here we show that DJ-1 is critical for disuse- induced skeletal muscle atrophy. Firstly, DJ-1 expression is positively correlated with muscle mass in human, and is decreased in atrophy muscle of immobilization mice and aged human. Secondly, DJ-1-deficient muscles are dystrophic, as well as impaired in activities and oxidative capacity. In disuse-atrophic condition, skeletal muscle specific-DJ-1 knockout mice show less cross section area (CSA) and more central nuclei than control mice. Thirdly, biochemical analysis indicates that these changes are due to enhanced activation of FoxO1, and subsequent upregulation of atrogenes. Finally, the inhibitor of DJ-1, compound 23, can mimic the effects of DJ-1 ablation in vivo. Our results illuminate that skeletal muscle DJ-1 has an unexpected role in the regulation of catabolic signals from mechanical stimulation, providing a therapeutic target for muscle-wasting diseases. Overall design: Gastrocnemius（gas） muscle tissues from immobilized muscle-specific DJ-1 knockout (MPARK7KO) mice and flox mice were extracted for RNA sequencing. The sequencing was conducted using Illumina BGIseq500 platform (BGI-Shenzhen, China). The transcriptomics data processing was addressed as previous article described. The clean reads were mapped to the reference genome (mm10) using STAR (2.7.10a). Quantification of gene expression was calculated using RSEM (v1.2.28). Subsequently, differential expression analysis between groups was conducted using the DESeq2(1.3.40) with adjust P value < 0.05 and |FC|>1.5. GO enrichment analysis and KEGG pathway analysis was performed by clusterProfiler (4.2.2) with different expression genes.