The intricate network of TFs, including SOX2, OCT4, NANOG, KLF4, c-MYC,β-catenin, STAT3, NF-κB, HIF-1α and YAP/TAZ, is central to the maintenance of the stem-likeproperties of GSCs, which in turn drive tumor heterogeneity, therapeutic resistance, andrecurrence. The gene discussed is KLF4; the disease is neoplasm.