Genomic studies in esophageal squamous cell carcinoma (ESCC), the predominant histological subtype in China, have identified mutations in several genes implicated in epigenetic regulations, such as KMT2D, KMT2C, KDM6A, EP300, and CREBBP, indicating that aberrations in epigenetic machinery play vital roles in ESCC initiation and progression [2]. The gene discussed is EP300; the disease is esophageal squamous cell carcinoma.