Consistent with these findings, radioresistant TE‐1R cells with TGM2, PYGB, and S100A6 knockdown were significantly more sensitive to IR compared to the control cells, underscoring the significance of TGM2, PYGB, and S100A6 for radioresistance in ESCC cells. Here, S100A6 is linked to esophageal squamous cell carcinoma.