Increased HRD1 activity, upon SIRT4-mediated SEL1L deacetylation, decreases the stability of mitochondrial protein alkylation B homolog 1 (ALKBH1), inducing mitochondrial damage in pancreatic ductal adenocarcinoma (PDAC).479 Treatment with entinostat, a SIRT4 stimulator, inhibits pancreatic cancer in vivo and in vitro.479,480 The myeloid-specific HRD1 complex has been implicated in the ubiquitination of STING, resulting in its degradation in the basal state and limiting its role in antitumor immunity.481. Here, SIRT4 is linked to familial pancreatic carcinoma.