KANK3 is a cytoskeletal regulator localized exclusively to vascular and lymphatic endothelial cells 1, where it functions as a tumor suppressor through multiple regulatory pathways. Structurally, KANK3 contains conserved KN motif and ankyrin repeat domains that enable interaction with Numb at sites of cell-cell contact, suggesting roles in cell adhesion and tissue integrity 2. At the molecular level, KANK3 mediates crosstalk between actin and microtubule cytoskeletons by localizing to focal adhesions and regulating the p38 MAPK signaling pathway 3, 4. KANK3 functions as a hypoxia-inducible proapoptotic target of p53, promoting apoptosis through AKT inhibition under hypoxic conditions 5. In lung adenocarcinoma and lung squamous cell carcinoma, KANK3 downregulation is associated with enhanced cell proliferation, invasion, and migration, while KANK3 restoration inhibits tumor growth and metastasis 4, 6. Clinical data reveal that reduced KANK3 expression in immune cells of lymphatic metastatic tissues and advanced tumor stages correlates with poor prognosis in head and neck and lung cancers 7, 6. These findings establish KANK3 as a cell-type-specific tumor suppressor candidate with therapeutic potential in multiple cancer types.