Here, we introduce the SUMO4:c.2T>C variant leading to SUMO4 haploinsufficiency as a novel potential genetic risk factor for ALS that possibly acts in conjunction with the oxidative stress-related factors trauma and cancer (plus radiochemotherapy), and provide evidence of an impact on SG dynamics and SUMOylation of VCP as similarly shown for mutations in the ALS-linked genes FUS and VCP [3–5, 7]. Here, VCP is linked to amyotrophic lateral sclerosis.