SNX3 (sorting nexin 3) is a retromer complex component that regulates endosomal trafficking and recycling of cargo proteins. As a phosphatidylinositol 3-phosphate (PtdIns3P)-binding protein, SNX3 mediates multivesicular body formation and is essential for recycling the Wnt morphogen transporter Wntless (WLS) from endosomes back to the Golgi 1. SNX3 assembles with an evolutionary conserved MON2-DOPEY2-ATP9A complex to facilitate WLS sorting and Wnt secretion 2. The SNX3-retromer pathway controls WNT signaling levels, as demonstrated by impaired WLS recycling and lysosomal degradation in SNX3-deficient cells, which causes neural tube closure defects in mice and correlates with human neural tube defects 3. In cancer biology, SNX3 plays a paradoxical role: it mediates EGFR recycling in triple-negative breast cancers, where low SNX3 and high EGFR levels correlate with poor survival and increased metastasis 4. Additionally, SNX3-retromer suppression by honokiol enhances cetuximab sensitivity in KRAS-mutant colorectal cancer by impairing lysosomal proteolysis and blocking autophagy and macropinocytosis 5. SNX3 expression is also regulated in osteosarcoma through the LINC01614-miR-520a-3p axis, affecting tumor progression 6.