Molecular insights and translational opportunities to enhance heat tolerance in rice

Heat stress is an increasingly serious threat to rice (Oryza sativa L.) productivity, yet the genetic and regulatory architecture underlying thermotolerance remain poorly resolved and fragmented across studies. Earlier research focused on individual pathways or specific developmental stages; however, recent advances now support an integrated understanding of heat stress adaptation in rice. This review synthesizes emerging insights into molecular physiology, regulatory signaling, epigenetic memory, and genome-scale variation associated with thermotolerance. We highlight the interconnected roles of calcium reactive oxygen species signaling, heat shock transcription factor networks, translational regulation, and chromatin-based stress memory in shaping reproductive-stage tolerance and maintaining grain quality under elevated temperatures. The review also emphasizes the value of pangenome analyses and structural variant discovery for identifying heat-responsive genes and regulatory elements absent from single-reference genomes. In addition, genome-wide association studies, haplotype-based breeding, genomic selection, and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-based genome editing are discussed as promising approaches for functional validation and deployment of favorable alleles controlling polygenic heat resilience. Despite these advances, several challenges continue to hinder translation into breeding-ready outcomes, including limited field-based validation of candidate genes, poor integration of multi-omics datasets into predictive breeding frameworks, and insufficient understanding of reproductive-stage regulatory networks. Furthermore, genotype × environment interactions, together with trade-offs among yield, grain quality, and stress resilience, strongly influence the stability and transferability of thermotolerance traits across diverse agroecological environments. By integrating mechanistic insights with genome-scale diversity and predictive breeding tools, this review outlines a genomics-enabled roadmap for developing heat-resilient rice cultivars under intensifying global warming and supporting sustainable global rice production.