Molecular mechanisms of cadmium uptake, translocation and detoxification in rice: Implications for breeding Cd-safe varieties

• Integrated molecular pathway details Cd perception, transport, and detoxification mechanisms while linking japonica - indica divergence to key alleles. • External modulation highlights how rhizosphere microbes and agronomic practices (water, pH, ion competition) actively reduce Cd bioavailability and uptake. • Synergistic strategies combine gene editing, allele mining, and tailored low-Cd cultivars optimized with agronomic and microbial management. Cadmium (Cd) contamination in rice severely threatens global food safety. Developing rice varieties with inherently low grain Cd content requires a comprehensive understanding of the genetic and molecular mechanisms controlling Cd absorption, translocation and detoxification, integrated with effective field management practices. This review synthesizes recent advances, highlighting cellular Cd perception as an initial trigger that activates signaling cascades coordinating detoxification responses, such as reactive oxygen species scavenging and glutathione-phytochelatin synthesis. We detail transporter-mediated processes (e.g., influx/efflux proteins) including root absorption, chelation and compartmentalization xylem loading, and phloem redistribution that govern Cd movement from soil to grain. The natural divergence in Cd accumulation between japonica and indica subspecies is attributed to allelic variation in key genes like OsHMA3, OsCd1 , and OsNRAMP5 . Furthermore, we overview the regulatory networks integrating transcription factors, miRNAs, and protein modifications that fine-tune Cd tolerance; crucially, these internal mechanisms are modulated by external factors such as the rhizosphere microbiome, which is shaped by root exudates, actively regulating Cd bioavailability through direct immobilization and indirect plant growth promotion. Concurrently, agronomic practices such as water management, soil pH adjustment, and competitive ion fertilization are effective strategies to minimize Cd phytoavailability and uptake. Building on this integrated soil-plant framework, we propose synergistic breeding strategies, including multi-omics-guided allele mining from wild germplasm, CRISPR-based multiplex editing of key transporter genes, and the development of cultivars that synergize with beneficial agronomic and microbial management. The combined application of these approaches offers a robust and sustainable path toward producing safe rice in Cd-impacted regions. This graph abstract illustrates the genetic, molecular, and ecological mechanisms underlying cadmium (Cd) absorption, translocation, and detoxification in rice, integrating the roles of both rhizosphere microbiota and ion competition. It highlights the role of cellular Cd perception in triggering signaling cascades that coordinate detoxification processes, transporter-mediated pathways, and compartmentalization mechanisms. Key regulatory networks involving transcription factors and miRNAs are depicted, emphasizing their role in fine-tuning Cd tolerance and accumulation. Additionally, the graph showcases the influence of rhizosphere microorganisms in modulating Cd dynamics through mechanisms such as biosorption and bioaccumulation.