In conclusion, EZH2 mainly through two action modes to regulate the development of AKI and CKD: 1) By catalyzing H3K27 trimethylation in the nucleus to silence numerous target genes, thereby affecting the expression or phosphorylation of target proteins and the activation of downstream signaling pathways (Wen et al., 2021; Liu et al., 2020); 2) EZH2 can also be localized to the cytoplasm and methylate non-histone proteins such as STAT3 (Zhou et al., 2016) and β-catenin (Wan et al., 2017). Here, EZH2 is linked to chronic kidney disease.