GPA33 (glycoprotein A33) is an Ig superfamily cell surface protein with dual roles in immune regulation and colorectal cancer (CRC) pathology. In the immune compartment, GPA33 is differentially expressed across multiple blood leukocyte subsets, with prominent expression on CD4+ T cells, particularly regulatory T cells (Tregs) and naive conventional CD4+ T cells 1. GPA33+ CD4+ central memory T cells maintain an undifferentiated state lacking immediate effector functions, suggesting a role in T cell differentiation and localization 1. While GPA33 has been investigated as a Treg-specific marker, it is not uniformly expressed across all Treg populations and cannot alone define regulatory function 2. In CRC, GPA33 serves as a promising therapeutic target, expressed on over 95% of primary and metastatic colorectal cancers 3. Expression shows intratumoral heterogeneity, correlating with differentiated phenotype and low WNT signaling, with antigen loss at tumor infiltrative edges 4. Clinical significance is substantial: GPA33-targeted radioimmunotherapy demonstrates therapeutic efficacy in preclinical models, with single-cycle 225Ac-DOTA-PRIT achieving histologic cures and improved survival 5. GPA33 also serves as a diagnostic immunohistochemical marker with 98-100% sensitivity for detecting metastatic CRC in pulmonary tissues 6. WNT inhibition induces GPA33 upregulation in GPA33-negative tumor cells, and GPA33-targeted CAR-T cell therapy shows promise for improved treatment 4.