Although the evidence supports the dual roles of proteases in carcinogenesis depending on cellular sources and the cancer microenvironment (9, 12, 13, 22, 23, 26, 34–36), the underlying molecular basis of PRSS3 for its pro- and antitumorigenic roles shown in different cancer types, even reported in the same type of cancer, such as in esophageal adenocarcinoma (24, 32), lung cancer (29, 35) and liver cancer (21, 36), remains elusive, causing many miscellaneous aliases to PRSS3 to impact its potential target-therapeutic applications (1, 12, 13, 23, 25, 36). Here, PRSS3 is linked to esophageal adenocarcinoma.