It has been reported that USP21 expression levels were dysregulated in a variety of human malignancies, including bladder cancer, breast cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, cholangiocarcinoma, lung cancer, pancreatic cancer, renal cell carcinoma, in which increased USP21 promoted the malignant phenotypes either by its activity of deubiquitinase to stabilize target proteins or via acting as a transcription factor to regulate the expression of target genes [14–25]. Here, USP21 is linked to familial pancreatic carcinoma.