Abstract: Mature red blood cells (RBCs), lacking nuclei and protein synthesis systems, were once considered devoid of functional RNA. However, recent studies have revealed abundant microRNAs (miRNAs) within RBCs, making their origin and function a research hotspot in hematology and molecular biology. This article reviews the paradigm shift from the "presence" to the "function" of RBC miRNAs, systematically discussing their roles in erythropoiesis, potential as disease biomarkers, mechanisms of intercellular communication, and clinical significance in transfusion medicine. RBC miRNAs are not merely "molecular archives" of erythroid differentiation but may also participate in various physiological and pathological processes through extracellular vesicle-mediated communication, such as in malaria infection, tumor microenvironment modulation, and self-regulatory feedback in erythropoiesis. Furthermore, dynamic changes in RBC miRNA profiles during blood storage provide novel molecular markers for assessing blood product quality. Future research, integrating high-throughput technologies like single-cell sequencing and spatial transcriptomics, will further unveil the translational potential of RBC miRNAs in disease diagnosis and therapy.

Key words: Mature red blood cells, MicroRNA, Extracellular vesicles, Biomarkers, Transfusion medicine