In NEDD4L CKO mice and ccRCC tissues, NEDD4L expression was inversely correlated with RAC2 expression, and NEDD4L directly reduced RAC2 protein levels, suggesting that aberrant NEDD4L expression may be a novel mechanism underlying RAC2 upregulation in renal cancer. Here, NEDD4L is linked to nonpapillary renal cell carcinoma.