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. Author manuscript; available in PMC: 2018 Jul 1.
Published in final edited form as: Bone. 2017 Jan 20;100:41–49. doi: 10.1016/j.bone.2017.01.017

Figure 1. Source of soluble Klotho.

Figure 1

The kidney is the main source of circulating Klotho under physiological conditions. Both renal proximal and distal tubules express membrane Klotho protein and may also produce a secreted Klotho protein through alternative splicing. The secreted Klotho only contains Kl1 domain and is directly secreted into the blood circulation. But its biologic function is not clear yet. Extracellular domain of membrane Klotho containing Kl1 and Kl2 repeats is shed and cleaved by secretases into either full extracellular domain or Kl1 repeat. Both cleaved Klotho fragments are present in the circulation. A few extra-renal organs including parathyroid gland and brain express Klotho protein as well, but their contribution to circulating Klotho in CKD/ESRD (dash line) remains to be confirmed.