SYVN1 and familial pancreatic carcinoma: 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