NRAMPs: Versatile Transporters Involved in Metal Ion Homeostasis and Their Applications in Rice Breeding

The NRAMP (natural resistance-associated macrophage protein) family plays a pivotal role in metal ion transport, regulating both essential micronutrient uptake (e.g., Fe, Mn, Zn) and toxic heavy metal accumulation (e.g., Cd, As, Pb) in plants. In rice ( Oryza sativa ), OsNRAMP transporters critically influence metal homeostasis, stress adaptation, and grain safety. Among them, OsNRAMP5 serves as a major entry point for Cd and Mn uptake, making it a prime target for low-Cd rice breeding. However, knockout of OsNRAMP5 leads to severe Mn deficiency, highlighting the need for precise genetic modifications (e.g. OsNRAMP5-Q337K) that reduce Cd accumulation while maintaining Mn nutrition. Additionally, OsNRAMP1 and OsNRAMP2 contribute to Cd translocation and plant immunity, whereas OsNRAMP3/4/6/7 participate in Mn, Fe, and Zn distribution and stress responses. This review systematically summarizes the structural, functional, and regulatory mechanisms of OsNRAMPs, emphasizing their roles in metal transport, pathogen resistance, and abiotic stress adaptation. Furthermore, we discuss strategies for developing low-Cd rice varieties, including QTL-based breeding, CRISPR/Cas9-mediated gene editing, and multi-gene stacking approaches. Finally, we outline future research directions, such as structural engineering of metal-binding sites and field validation of engineered rice lines, to ensure sustainable rice production in heavy metal-contaminated soils.