Here, we demonstrated that the GCN2-dependent AAR branch of the ISR is strongly activated in ADPKD models, and that it drives the transcription of ASNS, since silencing of GCN2 in Pkd1−/− cells is sufficient to restore lower levels of ATF4 and ASNS (Fig. 8). Here, PKD1 is linked to autosomal dominant polycystic kidney disease.