A matter of selectivity: ER-phagy suppression at the onset of pancreatic cancer.

KRAS mutations drive pancreatic ductal adenocarcinoma (PDAC). In this issue of Developmental Cell, Salomó Coll et al. reveal that KRAS suppresses endoplasmic reticulum (ER)-phagy in pancreatic acinar cells by inhibiting CCPG1 transcription. Impaired ER-phagy triggers protein aggregation, inflammation, and acinar-to-ductal metaplasia, promoting tumorigenesis. These findings highlight selective autophagy's role in cancer, with possible therapeutic implications.