Herein, we demonstrate that the autophagic tumour suppressor UVRAG represents a new bona fide MSI target gene in CRC and, likely, other MSI-related tumours, and that the truncating mutation in UVRAG enhances cellular transformation and penetrance of CRC tumour by interfering with the tumour-suppressing functions of UVRAGWT in a dominant-negative manner. Here, UVRAG is linked to neoplasm.