APLNR and lactic acidosis: ESM1 is a dermatan sulfate proteoglycan that modulates vascular permeability and angiogenesis [55], APLN and its only known receptor APLNR are essential for angiogenic sprouting and high glycolytic rate in ECs [56], and endothelial CAII expression is associated with a high-grade form of glial tumors with worse prognosis [57] likely by regulating TEC survival under lactic acidosis [58].