Taken together, we firstly clarified the low expression status of ZNF582 in ccRCC and its clinical value, revealed the regulatory effect of DNA methylation on ZNF582 expression, and elucidated a new mechanism by which ZNF582 overexpression up-regulates TJP2 protein expression, which leads to up-regulation of ERK2 protein and down-regulation of ERK2 protein phosphorylation, therefore suppressing ccRCC growth and metastasis (Fig. 8K). This evidence concerns the gene MAPK1 and nonpapillary renal cell carcinoma.