In addition, decreased levels of the E3 ubiquitin ligase HRD1 are found in AD, being this key enzyme expression regulated by XBP1s [327]; HRD1 not only has a role in managing ubiquitinated proteins for its degradation (such as Aβ), but also could target BACE1 or intervene in APP expression [326,327]. This evidence concerns the gene APP and Alzheimer disease.