These discrepancies might be due to the heterogeneity of ALS patients (sporadic vs. familiar), to the site of the biopsies (deltoid, tibialis anterior, vastus lateralis), duration of the pathology, site of onset, etc. R-SMADs enter into the nucleus through SMAD4, and in line with the work of Saris et al., we found a decreased Smad4 expression in muscle, suggesting a further site of dysregulation of TGFB intracellular signaling [93]. This evidence concerns the gene SMAD4 and amyotrophic lateral sclerosis.