In recent years, interest has arisen in the potential role of Klotho in the brain, including its possible protection of the central nervous system (CNS) and prevention of neurological diseases such as depression and the decline in cognitive function associated with aging.(105, 106) Indeed, high levels of Klotho originating in the choroid plexus are postulated to function as a gatekeeper at the interface between the brain and immune system in the choroid plexus.(107) Klotho depletion in aging or disease may weaken this barrier and promote immunomediated neuropathogenesis. This evidence concerns the gene KL and major depressive disorder.