Notably, LUSC shares essential transcriptional regulators—including SOX2, p63, KLF5, and GRHL2—with other SCCs, such as esophageal squamous cell carcinoma (ESCC) and head and neck squamous cell carcinoma (HNSCC).[19] These transcription factors play a pivotal role in orchestrating enhancer‐driven oncogenic programs, thereby modulating critical signaling pathways, including NFκB and the epithelial‐mesenchymal transition, both of which are vital in the pathogenesis of SCCs. The gene discussed is KLF5; the disease is esophageal squamous cell carcinoma.