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Figure 2. Klotho structure and multiple functions of Klotho. (A) Forms of Klotho protein: membrane-bound, soluble, and secreted. The membrane-bound form consists of KL1 and KL2. The extracellular domain can be cleaved by ADAM proteases, producing soluble Klotho. mRNA alternative splicing generates the secreted form of Klotho, which contains only the KL1 domain. (B) Systemic effects of Klotho on various organs and its role in reducing hypertrophy and fibrosis in the heart, improving kidney function, and enhancing cognition. Klotho exerts its effects through several pathways, including TGF-β, NF-κB, IGF-1, Wnt, and Nrf2.