Giampaola Trivellin and colleagues investigate the orphan G protein-coupled receptor (GPR101) for its possible involvement in corticotropinomas. They performed a set of analyses in children with sporadic Cushing Disease (CD) and revealed a rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD by sequencing analyses but their in vitro studies did not support a consistent pathogenic effect