PRAME (PReferentially expressed Antigen in MElanoma) functions as a substrate-recognition component of a Cul2-RING E3 ubiquitin-protein ligase complex, mediating target protein ubiquitination and degradation 1. The protein serves as a transcriptional repressor that inhibits retinoic acid receptor signaling through RARA, RARB, and RARG, preventing retinoic acid-induced cell proliferation arrest, differentiation, and apoptosis 2. PRAME is aberrantly overexpressed in various malignancies, particularly melanoma, where it shows diffuse nuclear immunoreactivity in 87% of metastatic and 83.2% of primary melanomas, contrasting with minimal expression (13.6%) in cutaneous nevi 3. In uveal melanoma, PRAME expression correlates with increased metastatic risk and serves as a prognostic biomarker when combined with gene expression profiling 4. The protein's cancer-specific expression pattern makes it valuable for differential diagnosis between malignant melanoma and benign melanocytic lesions 5. However, PRAME expression extends beyond melanoma to various epithelial and nonepithelial tumors, including endometrial carcinomas (82%), seminomas (78%), and synovial sarcomas (71%) 6. This broad expression pattern has therapeutic implications, as PRAME-targeted T cell receptor therapies show promising anti-tumor activity across multiple solid tumor types 7.