SYNPO2 (synaptopodin 2) is an actin-binding protein that primarily regulates cytoskeletal organization and cell migration. It promotes formation of nascent focal adhesions, actin bundles at the cell leading edge, and lamellipodia through Rho-ROCK cascade signaling 12. In muscle tissues, SYNPO2 localizes to Z-discs in striated muscle and dense bodies in smooth muscle, where it interacts with α-actinin, filamin C, and synemin to maintain contractile structure under mechanical stress 3. SYNPO2 functions as a critical checkpoint in vascular smooth muscle cells, preventing pathological phenotypic switching during arterial remodeling associated with atherosclerosis and aortic aneurysms 4. In cancer pathology, SYNPO2 shows context-dependent roles. Reduced expression correlates with poor hepatocellular carcinoma prognosis, with nuclear-cytoplasmic translocation via calcineurin promoting metastasis 5. Conversely, in colorectal cancer under hypoxia, SYNPO2 suppresses progression by inhibiting the YAP-KLF5 axis 6. In bladder carcinoma, elevated SYNPO2 promotes tumor development through mast cell infiltration and immunotherapy resistance 7. High SYNPO2 expression associates with poor survival in nasopharyngeal carcinoma 8. Additionally, SYNPO2 participates in selective autophagy pathways through BAG3 interactions 9 and may contribute to myofibrillar pathology 10.