MAGI3 is a membrane-associated scaffolding protein that functions primarily as a tumor suppressor through multiple signaling pathways. As a PDZ domain-containing protein, MAGI3 localizes to cell-cell junctions and regulates epithelial barrier function 1. MAGI3 suppresses cancer cell proliferation via at least three distinct mechanisms: (1) upregulating PTEN expression to inhibit PI3K/Akt signaling in glioma 2; (2) binding β-catenin through its PDZ domains to inhibit Wnt/β-catenin pathway activation in glioma and cervical cancer 34; and (3) functioning as an E3 ubiquitin ligase substrate-binding subunit that targets c-Myc for degradation in colorectal cancer 5. MAGI3 also regulates the MAS/ERK axis in renal cell carcinoma, with low expression associated with sunitinib resistance 6. In viral oncogenesis, HPV18 E6 targets MAGI3 for degradation, promoting cervical cancer progression through Wnt/β-catenin activation 4. Loss of MAGI3 expression correlates with poor prognosis across multiple cancer types. Importantly, MAGI3 can undergo premature polyadenylation in breast cancer, converting it from tumor suppressor to dominant-negative oncogene, a process potentially regulated by N6-methyladenosine modifications 7. MAGI3 also participates in developmental Wnt signaling through interactions with Gpr124 and Frizzled 8.