Acinar cell (AC)–specific Atg5 knockout mice develop pancreatitis regardless of alcohol feeding. BAC-Ela-Cre-; Atg5 f/f (Atg5 WT) and BAC-Ela-Cre+; Atg5 f/f (Atg5 KO) mice were injected with tamoxifen (75 mg/kg) once a day for consecutive 5 days, then treated with the Gao-binge alcohol model. (A) Total pancreatic lysates were subjected to immunoblot analysis. (B) Trypsin activity was measured from ethanol-treated pancreatic tissues. Data are mean ± SE (n = 5). **P < .01; Student’s t-test analysis. (C) Representative images of hematoxylin and eosin staining are shown. Arrowheads denote infiltrated inflammatory cells, omega shows pancreatic edema, asterisk indicates ADM), and delta represents cell death. Boxed areas were enlarged and showed in the lower panel. (D) Individual histology score of hematoxylin and eosin staining was graded and data are mean ± SE (n = 5–9). **P < .01; Student’s t-test analysis. (E) Representative images of Ly6B, CK19, and Sirius red staining are shown. (F) Representative EM images of Atg5 WT and Atg5 KO mice after alcohol are shown. Arrows denote enwrapped ZGs within autophagic vacuoles. LD, lipid droplet; NEU, neutrophil. Scale bar = 500 nm for Atg5 WT EtOH and 2 μm for Atg5 KO EtOH.