We first tested whether the IRE1 pathway is activated upon α-synucleinopathy in the photoreceptor neurons of Drosophila. We specifically overexpressed the human wild-type (WT) or two missence mutant forms (A30P and A53T) of α-synuclein identified from familial PD40,42 in the photoreceptor neurons. Here, ERN1 is linked to synucleinopathy.