Further analysis using clinical samples and TCGA datasets revealed that tumors with elevated levels of both LDHA and NUDT21, as well as increased K23-lactylated NUDT21, exhibit lower FDX1 levels, substantiating the role of the lactate-NUDT21-FDX1 axis in ESCC. Here, FDX1 is linked to esophageal squamous cell carcinoma.