Previous reports have indicated that DEF is predominantly localized in the nucleus and plays a crucial role in ribosome biogenesis and facilitating calpain3‐mediated degradation of p53 protein during digestive organ development.[17] Intriguingly, our study reveals significant cytoplasmic localization of DEF in pancreatic cancer cells, which is associated with its ability to promote tumor growth by stabilizing p65 independently of p53. This evidence concerns the gene TP53 and pancreatic neoplasm.