Our findings not only explain the newly reported tumorigenic role for KLF4 in breast carcinogenesis by the TCGA project, but they also provide the basis for future studies on how the precise expression level of KLF4 is orchestrated by coordination between ubiquitylation and methylation and how PRMT5 affects KLF4 function in other processes such as stem cell and cancer-initiating cell reprogramming. The gene discussed is PRMT5; the disease is cancer.