CRABP2 (cellular retinoic acid binding protein 2) is a dual-compartment protein that transports retinoic acid and regulates cellular processes through distinct subcellular mechanisms. In the nucleus, CRABP2 can promote tumorigenesis by interacting with and downregulating the tumor suppressor RB1 1. In the cytoplasm, CRABP2 demonstrates tumor-suppressive functions by interacting with AFG3L2 to promote mitophagy and enhance mitochondrial glutathione stability through the AFG3L2-SLC25A39 axis 1. However, CRABP2 also promotes cancer progression through multiple mechanisms, including TGF-β/Smad-mediated epithelial-mesenchymal transition (EMT) signaling and invadopodia formation, facilitating peritoneal metastasis in colorectal cancer 2. In melanoma, CRABP2 regulates cancer-associated fibroblasts (CAFs) infiltration and negatively correlates with immune checkpoint markers, with high expression predicting poor response to PD-1 inhibitors 3. CRABP2 serves as a prognostic biomarker across multiple cancers, with elevated expression associated with poor overall survival in lung cancer 4 and endometrial cancer 5. The protein can be targeted for degradation by PROTAC-mediated mechanisms involving TRIP12 and K29/K48-branched ubiquitin chains 6, suggesting potential therapeutic applications.