While ubiquitin is generally a signal for degradation, in the case of tauopathies it may also paradoxically act to worsen disease by stabilizing and promoting aggregation (20, 29), sequestering HDAC6 and other components of the autophagy pathway (112, 125–127), sequestering or inhibiting the proteasome (106, 107, 110, 111), or sequestering or overrecruiting VCP (13, 132). Here, HDAC6 is linked to tauopathy.