Though the explicit mechanism of tumorigenesis of REPS2 in ESCC is unclear, on the basis of our present study, we inferred that REPS2 was closely related to the RalBP1/RAC1/CDC42 signaling pathway through specific bindings with Ralbp1 which possesses the GAP activity for RACl and CDC42. This evidence concerns the gene REPS2 and esophageal squamous cell carcinoma.