In spite of the well described role of E2f1 in the modulation of both apoptosis and autophagy, mainly in melanoma and embryonic cell lines, the upregulated levels of E2f1 found in the skeletal muscle from SOD1G93A mice at P60 could not be sufficient enough to prompt the activation of LC3 and, above all, Beclin1 and Atg5. At protein level, the lower ratio LC3-II/LC3-I and an absence of increased LC3-II level suggested a decreased autophagosome formation and therefore a lack of autophagy activation in SOD1G93A mice. The gene discussed is E2F1; the disease is melanoma.