We found that (1) GPR37L1 expression does not change the basic membrane properties of hippocampal astrocytes or neurons, (2) GPR37L1 mRNA expression is upregulated in ischemia in vivo, (3) GPR37L1 expression and signalling activated by its ligand prosaptide are neuroprotective in ischemic brain slices, and (4) prosaptide‐evoked GPR37L1‐signalling inhibits glutamate transporters in astrocytes and reduces neuronal NMDAR activity. This evidence concerns the gene GPR37L1 and ischemia.