With a depth of more than 6000 proteins, our analysis covers three times more proteins compared to a previous study performed on an immortalized myoblast cell line (C2C12 cells) (Tannu et al., 2004; Kislinger et al., 2005). By using five independent primary myoblast lines, we were able to take into account the variability that typically affects primary cultures and derive robust and reproducible proteome signatures (Hindi et al., 2017; Kim et al., 2020). Our data highlight hundreds of changes in energy metabolism, RNA and protein synthesis, as well as cytoskeletal organization that occur with specific temporal dynamics during myogenic differentiation. RUVBL1 participates in various complexes, including INO80, NuA4, SWR1, TIP60-P400, PAQosome (R2TP), as a transcriptional and/or chromatin modifier, with or without its homologue RUVBL2 (Gorynia et al., 2011; Chen et al., 2015; Lakisic et al., 2016). We have observed that the localization of SIRT1 changes dynamically during myogenic differentiation, and that the interaction between SIRT1 and LMOD1 increases during the initial stages of myogenic differentiation.