Two mutations responsible for loss of surface expression in GPR56, causing bilateral frontoparietal polymicrogyria (BFPP), are the highly conserved C346SS10.47 and W349SS10.50 refs. 7,74,75 More generally, our approach promotes future experiments focusing on the central role of GAIN domains in the physiological functions of aGPCRs and PKD1 molecules and will aid analyses of how structural anomalies contribute to their dysfunction under disease conditions. The gene discussed is PKD1; the disease is polymicrogyria.