There is mounting evidence that dysregulation of UPR or chronic ER stress is a fundamental process in neurodegenerative disorders associated with insoluble protein aggregate formation (Matus et al., 2011) and UPR impairment plays a critical role in the development of tauopathies in that activated UPR enhances tau phosphorylation tau contributing to the formation of neurofibrillary tangles (Fu et al., 2010; Nijholt et al., 2012; Park et al., 2009; Resende et al., 2008). Here, MAPT is linked to tauopathy.