MYPT1/PP1 is identified as the specific protein phosphatase for dephosphorylating histone methyltransferase enhancer of zeste homolog 2 (EZH2) at S21 residue, demonstrating that EZH2 dephosphorylation/EZH2‐S21A expression causes global changes in multiple families of genes implicated in epithelial‐mesenchymal transition (EMT), contributing to fibrotic diseases, and revealing that AKT‐EZH2‐H3K27Me3 signal axis plays an important role in lens EMT induced by TGFβ and mediates pathogenesis of anterior subcapsular cataract (ASC). Here, EZH2 is linked to Tako-tsubo cardiomyopathy.