Interestingly, a recent study identified MLN4924, an inhibitor of the NEDD8-activating enzyme (NAE), as a compound that improves motor neuron viability and neuronal activity in iPSC-derived ALS models with TARDBP mutations, highlighting the therapeutic potential of targeting the NEDD8 pathway in ALS and calling for further investigation into its role in TDP-43 proteinopathies [148]. Here, TARDBP is linked to amyotrophic lateral sclerosis.