ZUP1 and nervous system disorder: The involvement of DUBs in neurological diseases may happen by a three-step process: (1) direct mutations in the gene encoding the DUB; (2) a central role for the DUB in a ubiquitin-dependent quality control pathway implicated in disease; and (3) involvement of the DUB in handling a specific substrate that is critical to a neurodegenerative disease process (Figure 1).