CTSS and neurodegenerative disease: The expression of cathepsins, the important executors of lysosomal degradation, was deregulated in cells of neurodegenerative diseases, and they showed reduced efficiency in degrading misfolded proteins and deregulated expression.14,175 For example, cathepsin D, the hydrolase responsible for degrading HTT, was identified to be less effective in degrading mHTT, the aggregation- prone HTT mutant in HD.14,176 It is worth noting that cathepsins do not always play a protective role.