PKM and ischemia: Lactate, previously regarded as a waste product of glycolysis, has received extensive attention as a regulator of multiple molecular processes.[27] Lactate can function as a signaling molecule to affect behavior, shape the gut microbiome to alter thermogenesis, and promote PD‐1 expression in regulatory T cells to blunt tumor treatment.[28] EC‐derived lactate controls adult hippocampal neurogenesis, muscle regeneration following ischemia, and pathological retinopathy.[10, 29] We found that blood lactate levels were decreased in mice with EC‐specific deletion of Pkm2 and in OVX mice.