We identified four SUMO E3 ligases whose knockout consistently reduced the levels of stress-induced TDP-43 SUMOylation: EGR2 (KROX20), PIAS1, TRIM28 (KAP1), and ZNF451 (ZATT). EGR2 is linked to the neuromuscular disorder Charcot Marie Tooth Disease and is an immediate early gene rapidly reacting to external cellular stimuli aligning with the early response of TDP-43 SUMOylation upon stress [66, 80]. Here, PIAS1 is linked to Charcot-Marie-Tooth disease.