Interestingly, associated genes of UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers (UBE2V1, UBE2V2 and UBE2NL) were also found among this cluster, which catalyzes synthesis of non-canonical polyubiquitination that does not lead to degradation by proteasome but rather downstream inflammatory responses [67], suggesting the mechanisms of UPS dysfunction in the development of AD are likely more complicated. Here, UBE2NL is linked to Alzheimer disease.