Increased understanding of the functions of lactate has suggested a close relationship between lactate homeostasis and normal brain activity because of its importance as an energy source and signaling molecule. Here we show that lactate levels affect adult hippocampal neurogenesis. Cerebrovascular-specific deletion of PTEN causes learning and memory deficits and disrupts adult neurogenesis with accompanying lactate accumulation. Consistently, administering lactate to wild-type animals impairs adult hippocampal neurogenesis. The endothelial PTEN/Akt pathway increases monocarboxylic acid transporter 1 (MCT1) expression to enhance lactate transport across the brain endothelium. Moreover, cerebrovascular overexpression of MCT1 or deletion of Akt1 restores MCT1 expression, decreases lactate levels, and normalizes hippocampal neurogenesis and cognitive function in PTEN mutant mice. Together, these findings delineate how the brain endothelium maintains lactate homeostasis and contributes to adult hippocampal neurogenesis and cognitive functions. Display omitted •Brain ECs maintain adult hippocampal neurogenesis by regulating lactate homeostasis•Loss of endothelial PTEN or MCT1 impairs hippocampal neurogenesis and cognition•The PTEN/Akt pathway upregulates MCT1 to transport lactate across the brain endothelium•PTEN mutant mouse phenotypes are rescued by MCT1 overexpression or Akt1 deletion Lactate is increasingly recognized as an important signaling molecule in the brain. Wang et al. show that the PTEN/Akt pathway in endothelial cells upregulates MCT1 to enhance lactate transport across the brain endothelium, which is critical for lactate homeostasis, adult hippocampal neurogenesis, and cognitive function.