Pancreatic cancer remains one of the leading causes of cancer-related mortality worldwide. The role of p53 family isoforms in the pathogenesis of human cancer has been under the radar for decades, mainly due to the significant structural homology of p63 and p73 genes with the notorious p53 gene. Both p63 and p73 have two main isoforms, transactivating (TA) and deltaN (DN), each of which has been studied in normal and cancer cells. Although their role in cancer remains elusive and is tissue-specific, the manner in which they act in pancreatic cancer is evident. As for p53, the mechanism of its gain-of-function activities in pancreatic cancer is now better understood. In this review, the role of each gene and their isoforms is discussed, as well as the possible therapeutic agents for pancreatic cancer. Currently, the science revolving around p53 family isoforms focuses on their specific roles. Thus, we propose that future research be directed at studying the interaction between the isoforms, as well as accelerating the assessment of potential therapeutic agents. Contents 1. Introduction 2. Structure of p53 family isoforms 3. Role of p53 mutations in pancreatic cancer 4. Role of p63 isoforms in pancreatic cancer 5. Role of p73 isoforms in pancreatic cancer 6. Therapeutic targets of pancreatic cancer 7. Conclusion and future directions