Lu et al. (2020) demonstrated that small EVs derived from brain-metastatic breast cancer cells decrease the expression of tight junction proteins (ZO-1, Claudin-5) between BMECs by transporting lncRNA GS1-600G8.5, increasing BBB permeability. However, the downstream targets of lncRNA GS1-600G8.5 are unknown. These studies demonstrate the significance of decreased tight junction protein expression levels caused by small EVs inclusions in BBB disruption and are expected to be a predictor of breast cancer brain metastasis (Figure 3D). Here, CLDN5 is linked to breast carcinoma.