Introduction: Synaptopodin 2 (SYNPO2) is a functioning protein. It has been detected in many malignancies. But the relation between SYNPO2 and breast cancer (BC) is unclear.
Materials and methods: In this study, we explored the expression and function of SYNPO2 in BC. We found that SYNPO2  gene in BC was downregulated at the transcriptional level in both validated and TCGA cohorts. 
Results: The results revealed that age, lymph node metastasis, and clinical stage in the validated cohort were related to the expression of SYNPO2 negatively. Kaplan–Meier analysis showed that patients with lower SYNPO2 expression had a worse overall survival. 
Discussion: We found that migration and invasion were promoted after knocking down SYNPO2 in MCF-7, MDA-MB-231, BT-549, and MDA-MB-468. Meanwhile, knockdown of SYNPO2 could enhance PI3K/AKT/mTOR signaling pathway, which may induce migration and invasion. Our findings reveal that SYNPO2 was associated with BC.
Keywords: breast cancer, SYNPO2, metastasis, PI3K/AKT/mTOR signaling pathway