Based on this feature of ENT3, we propose a pathogenic model for MNGIE: cytoplasmic accumulation of thymidine and deoxyuridine caused by TP deficiency enters mitochondria on the one hand, leading to imbalance of mitochondrial nucleoside levels and disruption of mtDNA homeostasis, and on the other hand, it causes excessive accumulation of nucleosides in lysosomes, resulting in lysosomal dysfunction. The gene discussed is SLC29A3; the disease is mitochondrial neurogastrointestinal encephalomyopathy.