F-box proteins are key components of SCF (Skp1-Cullin1-F-box protein) complexes, which exert E3 ubiquitin ligase activity and participate in cell cycle and signal transduction. F-box proteins interact with Skp1 through the F-box domain and with proteins to be ubiquitinated through other interaction domains. We have characterized a novel muscle-specific F-box protein, FBXO40, the expression of which decreases in the dystrophic muscle of Limb-girdle muscular dystrophy (LGMD) patient. During the development of skeletal muscle, FBXO40 can only be detected at postnatal stage from about 2 weeks after birth. By overexpressing in C2C12 cells, FBXO40 localized in cytoplasm. Most importantly, the expression of FBXO40 can be upregulated in skeletal muscle from denervation- but not starvation-related muscle atrophy. All our data suggest that FBXO40 may function as a regulator involved in the postnatal myogenesis.