Several disease states (cancer, sepsis...) are frequently associated withderegulated protein homeostasis. The main consequence is muscle wasting that strongly contributes to the deterioration of patient’s health and compromises treatments. To date there is no valid therapy to reduce or prevent this deregulation. Thus, reducing myofibrillar protein loss during catabolic states is a major challenge. B6 showed that the muscle-specific TRIM63/MuRF1 targets muscle contractile proteins and energy enzymes for degradation in catabolic states through defined TRIM63/MuRF1-E2 complexes9. Thus, such complexes represent potential therapeutic targets. Employing in vitro and in vivo model systems, this task will identify specific TRIM63/MuRF1-E2 pairs implicated in muscle atrophy and elaborate pharmacological drugs for inhibiting the complex for fighting against patient’s weakness