Significance Genetic factors play a major role in the development of human addiction. Identifying these genes and understanding their molecular mechanisms are necessary first steps in the development of targeted therapeutic intervention. Here, we have isolated the gene encoding Ras suppressor 1 (Rsu1) in an unbiased genetic screen for altered ethanol responses in the vinegar fly, Drosophila melanogaster . Our behavioral, genetic, and biochemical experiments show that Rsu1 links signaling from the integrin cell adhesion molecule to the small GTPase Rac1 in adult neurons to regulate actin dynamics and alcohol consumption preference. We also show that variants in human RSU1 associate with altered drinking and brain activation during a reward prediction task, thereby validating the predictive power of our approach.