We analyzed the effects of the POAG- and ALS-associated mutants of OPTN on the LUBAC- and TNF-α-mediated NF-κB activation in HEK293T cells, and showed that the ALS-associated OPTN mutants lost their ability to suppress NF-κB activation, mainly due to the dysfunction in the UBAN domain of OPTN [121]. The gene discussed is TNF; the disease is amyotrophic lateral sclerosis.