The Ubiquitin Proteasome System (UPS) is the major actor of muscle wasting during various physio-pathological situations. In the past 15 years, increasing data have depicted a picture, although incomplete, of the mechanisms responsible for in myofibrillar protein degradation, from the discovery of muscle-specific E3 ligases to the identification of the signaling pathways involved. The targeting specificity of the UPS relies on the capacity of the system to first recognize and then label the proteins to be degraded with a polyubiquitin (polyUb) chain. It is fairly assumed that the recognition step is accomplished by the numerous E3 ligases present in mammalian cells. The E3 ligase MuRF1 is so far the only enzyme known to direct different contractile proteins for degradation, i.e. troponin I, myosins and actin. However, like most E3s, MuRF1 does not possess any catalytic activity and depends on the activity of cognate E2 enzymes. The latter may be more than simple Ub-providers for E3s and they are probably important actors in the ubiquitination machinery. Surprisingly, while most efforts were put on E3s, the exact role of E2s in muscle protein degradation is still largely ignored. Amongst the 37 E2s described in humans, a very limited number have been addressed for their implication in skeletal muscle protein degradation and the vast majority of studies were only descriptive. Thus, we aim at identifying E2 enzymes that may be implicated in the ubiquitination of contractile proteins during skeletal muscle atrophy