Recently, it is believed that the loss of Smad4 itself may not directly initiate tumor formation, but it can promote tumor progression initiated by other genes, such as KRAS activation in pancreatic ductal adenocarcinoma and APC inactivation in colorectal cancer, indicating that Smad4 plays different roles in different tumors [8]. The gene discussed is SMAD4; the disease is pancreatic ductal adenocarcinoma.