By generating SOD1 mice with a skeletal muscle-specific deletion of HDAC4 (namely SOD1 HDAC4mKO mice), we recently demonstrated that, in male mice, deletion of HDAC4 in the skeletal muscle worsens the pathological features of ALS, advancing and exacerbating both body weight and skeletal muscle loss, in addition to negatively affecting neuromuscular junction integrity and muscle innervations [19]. The gene discussed is SOD1; the disease is amyotrophic lateral sclerosis.