Klotho is an anti-aging single-pass membrane protein that is mainly produced in the kidney. The level of soluble klotho decreases with age and the klotho gene is associated with an increased risk of age-related diseases, such as diabetes, skin atrophy, chronic kidney disease, ataxia and cancer.
The klotho gene is composed of five exons and encodes a membrane glycoprotein located in the plasma membrane.
The 3 forms of klotho protein have a specific function:
1-klotho forms a complex membrane protein with fibroblast growth factor receptors (FGFR) and acts as a binding cofactor for FGF₂₃, which is involved in the regulation of aging and the development of chronic diseases through the regulation of ionized phosphorus and vitamin D metabolism.
2- Secretory klotho as a humoral agent has pleiotropic activity which includes regulation of oxidative stress, growth factor signaling and ion homeostasis. Secretory klotho also plays a role in organ protection.
3- The intracellular form of Klotho suppresses inflammation caused by cellular aging and mineral metabolism.