The E2 of UBE2E3 (UbcH9), E3s such as parkin, VHL/Cul2, Znf179 (RNF112), Praja1, RNF220, and SCFcyclin F, and DUBs such as USP5, USP7, USP8, USP10, USP13, USP14, and CYLD, are reportedly involved in the ubiquitination and deubiquitination of TDP-43 (Tran and Lee 2022), indicating that many E3s and DUBs regulate the spatiotemporal ubiquitin dynamics of TDP-43 in ALS. This evidence concerns the gene UBE2E3 and amyotrophic lateral sclerosis.