NFE2L2 and esophageal squamous cell carcinoma: <b>Results</b>: Using genetically defined isogenic ESCC cell models, we show that activation of mutant NRF2 (NRF2<sup>Mut</sup>) or wild-type NRF2 (NRF2<sup>WT</sup>) produces distinct, context-dependent effects on squamous differentiation, proliferation, and therapeutic response.