The disclosure relates to treating muscle wasting-associated disorders in a patient, using a therapeutically effective amount of an antagonist of Fbxo40, wherein the antagonist reduces the expression, level or activity of Fbxo40. The Fbxo40 antagonist increases muscle mass, or prevents, limits or reduces muscle mass loss, in the patient. The Fbxo40 antagonist can be a low molecular weight (LMW) compound, a protein, an antibody, or an inhibitory nucleic acid, such as a siRNA. The disclosure also relates to methods of screening for antagonists of Fbxo40, and methods of diagnosing or monitoring levels of muscle mass maintenance, loss or increase.