In contrast, it was reported that both monoubiquitylation and polyubiquitylation contribute to the formation of insoluble protein inclusions present in neurodegenerative diseases (Dickey et al., 2006; Tan et al., 2008) and, as mentioned above, increased aggregation of tau was detected in a cell culture overexpressing CHIP (Petrucelli et al., 2004) implying that ubiquitylation enhances the formation of these aggregates. Here, MAPT is linked to neurodegenerative disease.