Abstract: α-Klotho protein (KL) has been discovered more than 20 years ago, and immediately emerged as a master regulator of aging-related processes, which basically operates as an anti-aging factor. It is expressed through the entire human body, representing the choroid plexus and the kidney as the most active sources at the central nervous system (CNS) and periphery level respectively. To a lesser extent, also the parathyroid gland, the adipose tissue, and the liver express KL.