Although OPTN reportedly functions as an autophagy receptor, we determined that the ALS-associated OPTN mutations, E478G and Q398X, abrogated the inhibitory effects of OPTN on LUBAC-mediated NF-κB activation, and accelerated TNF-induced cell death in HEK293T and HeLa cells [121]. Here, NFKB1 is linked to amyotrophic lateral sclerosis.