The study investigates the export of microRNAs (miRNAs) and microRNA-protective proteins by mammalian cells. It was found that after serum deprivation, several human cell lines export a significant amount of miRNAs into the culture medium, which is largely energy-dependent. These exported miRNAs are found in both microvesicles and exosomes, as well as in the supernatant fraction. The authors identified candidate proteins involved in this process, including nucleophosmin 1 (NPM1), which may play a role in protecting extracellular miRNAs from degradation. The results suggest a previously unrecognized miRNA trafficking system in mammalian cells, consistent with the hypothesis of cell-cell communication mediated by miRNAs. The study also highlights the complexity of miRNA distribution and packaging, indicating the existence of multiple pathways for miRNA export and suggesting that miRNAs may have a broader role in cellular communication than previously thought.The study investigates the export of microRNAs (miRNAs) and microRNA-protective proteins by mammalian cells. It was found that after serum deprivation, several human cell lines export a significant amount of miRNAs into the culture medium, which is largely energy-dependent. These exported miRNAs are found in both microvesicles and exosomes, as well as in the supernatant fraction. The authors identified candidate proteins involved in this process, including nucleophosmin 1 (NPM1), which may play a role in protecting extracellular miRNAs from degradation. The results suggest a previously unrecognized miRNA trafficking system in mammalian cells, consistent with the hypothesis of cell-cell communication mediated by miRNAs. The study also highlights the complexity of miRNA distribution and packaging, indicating the existence of multiple pathways for miRNA export and suggesting that miRNAs may have a broader role in cellular communication than previously thought.