Emerging evidence indicates that KLF4 orchestrates the topological reorganization of enhancer‐based TADs and genome‐wide enhancer rewiring,[49] in addition to directly interacting with and recruiting CREBBP.[50] However, in differentiated or cancer cells, KLF4 alone may be insufficient for CREBBP recruitment, enhancer activation, or chromatin architectural reorganization, suggesting the need for additional architectural factors or co‐regulators. The gene discussed is CREBBP; the disease is cancer.