RAI2 (retinoic acid induced 2) is a transcriptional coregulator that functions as a tumor suppressor across multiple cancer types. The protein contains a novel proline-rich domain and is expressed in various fetal and adult tissues including brain, heart, lung, and kidney 1. RAI2 acts as a master corepressor by binding to CtBP transcriptional regulators through repetitive short linear motifs (SLiMs), inducing CtBP polymerization and nuclear foci formation, which relieves CtBP's corepressor function 2. In cancer biology, RAI2 demonstrates critical tumor suppressor activities: it maintains genomic stability by ensuring mitotic fidelity and proper chromosome X 3, suppresses cell proliferation, migration, and invasion while inducing apoptosis 4, and prevents early hematogenous dissemination of cancer cells to bone marrow 5. Low RAI2 expression is associated with poor prognosis in multiple cancer types including breast, prostate, gastric, and colorectal cancers 674. The protein functions through multiple pathways including inhibition of AKT signaling 45 and regulation of DNA damage response pathways 3. RAI2's expression is regulated by promoter methylation in colorectal cancer, where methylation serves as an independent poor prognostic marker 4.