We recently identified and characterized super-enhancer-associated genes with lineage-specific expression patterns in esophageal SCC (ESCC)13,14, including TP63 and SOX2. Previous investigations have shown that deletion of TP63 causes striking defects in epidermal development, highlighting its key role in the regulation of squamous cell differentiation and proliferation15–17. Here, TP63 is linked to esophageal squamous cell carcinoma.