PRRG1 (proline rich and Gla domain 1) is an X-linked transmembrane protein containing vitamin K-dependent gamma-carboxyglutamic acid (Gla) modifications that localize it to the plasma membrane 1. Functionally, PRRG1 interacts with the HECT E3 ligase NEDD4 via its C-terminal PPXY motif, promoting NEDD4 self-ubiquitination and reducing its protein levels, thereby stabilizing the oncoproteins KRAS and EGFR 1. This mechanism enhances downstream signaling and macropinocytosis under nutrient-deprived conditions. PRRG1 is dysregulated across multiple cancers with disease-relevant consequences. It is downregulated as a miR-17-92 cluster target in hepatocellular carcinoma, negatively correlating with miRNA expression 2. Conversely, PRRG1 is significantly upregulated in pancreatic ductal adenocarcinoma (PDAC), where elevated expression correlates with poorer patient survival 1. PRRG1 knockdown reduces PDAC cell proliferation and tumor growth in vivo 1. PRRG1 is also elevated in gestational diabetes mellitus, where knockdown enhances cell viability and migration 3. Clinically, PRRG1 serves as a prognostic biomarker in multiple malignancies, including gliomas 4 and breast cancer 5, where it contributes to multi-gene risk signatures. The vitamin K-dependence of PRRG1 enables pharmacological targeting via warfarin, a clinical vitamin K antagonist, suggesting therapeutic repurposing potential in PDAC 1.