In conclusion, our evidence reported here supports the notion that the upregulation of ALDH1L2 is key to the formation of cancer stem cells of the U251 glioblastoma cells, and its function appears to be related to the production of NADPH via the utilization of 1C-units delivered by mitochondria 10-formyl THF. This evidence concerns the gene ALDH1L2 and glioblastoma.