Crystal structure analyses revealed that the OPTN-UBAN domain selectively binds to the linear ubiquitin chain in a similar manner to the NEMO-UBAN domain9, and that the ALS-associated E478 residue is essential for specific linear ubiquitin recognition, but not K63-linked ubiquitin, as no important interaction seems to occur between E478 and K63-linked ubiquitin, as deduced from the structure of NEMO-UBAN K63 diubiquitin (Fig. 2c–e and Supplementary Fig. 5). Here, OPTN is linked to amyotrophic lateral sclerosis.