KL and Cognitive impairment: The function of Klotho in the brain was initially derived from klotho (OMIM 604824) knockout mice that demonstrated cognitive impairment, premature death, and synaptic loss.1,2 Conversely, overexpression of klotho extends the lifespan, improves cognitive function, and reduces age-associated phenotypes in mice.3,4 A common haplotype consisting of 6 missense variants in the human Klotho gene is termed KL-VS.