In summary, the results of the untargeted differential proteomics analysis supported the execution of further hypothesis-driven experiments, which eventually demonstrated that, downstream to the overexpression of MyBP-H in ALS, there was a change in the pattern of PTMs (i.e., phosphorylation) of proteins involved in muscular actin–myosin regulation. This evidence concerns the gene MYBPH and amyotrophic lateral sclerosis.