A cis-regulatory allele of ZmNPR1I spatially uncouples flowering from stalk-rot resistance in maize.
Pleiotropic effects of adaptive genes frequently constrain crop improvement by coupling beneficial traits with unfavorable trade-offs. In maize, ZmCCT10 confers strong stalk-rot resistance but causes delayed flowering under long-day conditions, limiting its deployment in temperate breeding. Here, we identify qPss3 as a cis-regulatory locus that governs its downstream target gene, ZmNPR1I. The ZmNPR1I protein represses ZmCCT10 transcription and, together with ZmNPR1-3, facilitates ZmCCT10 protein degradation. The favorable qPss3A5 allele reduces ZmNPR1I expression in leaves, relieving repression of ZmCCT10, ZmSPL32, and ID1, which collectively enhance ZCN8 expression to accelerate flowering. In roots, however, pathogen-induced activation of the resistant ZmCCT10H5 allele largely bypasses qPss3 regulation, thereby preserving stalk-rot resistance. Introgression of qPss3A5 into ZmCCT10H5-containing maize germplasm restores flowering adaptation without compromising disease resistance, improving yield stability under disease pressure. Our work reveals a tissue-specific qPss3A5-ZmNPR1I regulatory module that uncouples the developmental and immune functions of a pleiotropic adaptive gene, providing a general strategy for optimizing beneficial alleles in crop breeding.