There are a total of 33 members of adhesion G protein-coupled receptors (GPCRs) in humans and 30 members in mice and rats. More than half of these receptors are expressed in the central nervous system (CNS), indicating their possible roles in the development and function of the CNS. Indeed, it has been shown that adhesion-GPCRs are involved in the regulation of neurulation, cortical development and neurite growth. Among the few adhesion-GPCRs being studied, GPR56 is so far the only member associated with a human brain malformation called bilateral frontoparietal polymicrogyria (BFPP). The histopathology of BFPP is a cobblestone-like brain malformation characterized by neuronal overmigration through a breached pial basement membrane (BM). Further studies in the Gpr56 knockout mouse model revealed that GPR56 is expressed in radial glial cells and regulates the integrity of the pial BM by binding a putative ligand in the extracellular matrix of the developing brain.