Although a high expression of the ATX gene (ENPP2) correlates with a poor outcome in several types of cancer (such as B-cell lymphomas, renal cell carcinomas, liver or pancreatic cancers [27,28,29]), it is now well established that the tumor microenvironment is an essential source of ATX [30]. Here, ENPP2 is linked to hereditary clear cell renal cell carcinoma.