The mutant PLP1 protein associated with mild PMD phenotypes appear to be cleared quickly from the ER, via the proteasomal degradation pathway and/or ER exit, while the mutant PLP1 protein associated with severe PMD phenotypes is resistant to protein degradation and/or exclusion from the ER, triggering UPR activation (Roboti et al., 2009). Here, PLP1 is linked to Pelizeaus-Merzbacher spectrum disorder.