The IPA1–NRT1.1B regulatory module regulates ROS homeostasis to confer cadmium tolerance in rice

• Cadmium (Cd) is a highly toxic heavy metal that poses serious threats to rice ( Oryza sativa L.) production and human health due to its bioaccumulation in edible tissues. • we investigated the molecular mechanisms of Cd tolerance in rice, focusing on IPA1, NRT1.1b , and SAPK6 . A phenotypic analysis revealed that all of the ipa1, nrt1.1b , and sapk6 mutants displayed enhanced sensitivity to Cd stress, as indicated by the excessive accumulation of reactive oxygen species. • Mechanistically, IPA1 positively regulated NRT1.1b expression, and site-directed mutagenesis of its phosphorylation sites (S201 and S213) significantly impaired its ability to bind and activate NRT1.1b . • Consistent with previous studies, OsSAPK6 interacted with, and phosphorylated IPA1 , which may fine-tune its transcriptional activity. • Collectively, these results suggested that the IPA1–NRT1.1b–SAPK6 regulatory module contributed to Cd tolerance by modulating reactive oxygen species homeostasis, providing new insights for breeding low-Cd rice cultivars. Cadmium (Cd) is a highly toxic heavy metal that poses serious threats to rice ( Oryza sativa L.) production and human health due to its bioaccumulation in edible tissues. Here, we investigated the molecular mechanisms of Cd tolerance in rice, focusing on IPA1, NRT1.1b , and SAPK6 . A phenotypic analysis revealed that all of the ipa1, nrt1.1b , and sapk6 mutants displayed enhanced sensitivity to Cd stress, as indicated by the excessive accumulation of reactive oxygen species. Mechanistically, IPA1 positively regulated NRT1.1b expression, and site-directed mutagenesis of its phosphorylation sites (S201 and S213) significantly impaired its ability to bind and activate NRT1.1b . Consistent with previous studies, OsSAPK6 interacted with, and phosphorylated IPA1 , which may fine-tune its transcriptional activity. Collectively, these results suggested that the IPA1–NRT1.1b–SAPK6 regulatory module contributed to Cd tolerance by modulating reactive oxygen species homeostasis, providing new insights for breeding high-Cd tolerance rice cultivars.