We observed that blockage of proteasomal degradation increased the levels of MRE11A (Fig. 3I,J), consistently with the observations as shown Fig. S3A. We concluded that UBQLN4‐OV in ESCC leads to an accelerated MRE11A degradation by targeting ubiquitinated‐MRE11A for proteasomal degradation. Here, MRE11 is linked to esophageal squamous cell carcinoma.