In mice, Cldn5 ablation enhanced BBB permeability and allowed infiltration of large proteins up to ∼69 kDa (e.g., IL-6) into mouse brain parenchyma and was associated with depressive-like behavior and behavioral impairments characteristic of schizophrenia and depression (Menard et al., 2017; Greene et al., 2018; Ma et al., 2018). The gene discussed is CLDN5; the disease is major depressive disorder.