The antiaging protein of Klotho is a transmembrane protein mainly expressed in 
the kidney, parathyroid glands and choroid plexus of the brain. The Klotho 
protein exists in two forms, a full-length membrane form and a soluble secreted 
form. The extracellular domain of Klotho can be enzymatically cleaved off and 
released into the systemic circulation where it acts as β-glucuronidase and a 
hormone. Soluble Klotho can be found in the blood, cerebrospinal fluid, and the 
urine of mammals. Klotho deficiency results in early appearance of multiple 
age-related disorders and premature death, whereas overexpression of Klotho 
exerts the opposite effect. Klotho may influence cellular transport processes 
across the cell membrane by inhibiting calcitriol (1,25(OH) (2)D(3)), formation 
or by directly affecting transporter proteins, including ion channels, carriers 
and pumps. Accordingly, Klotho protein is a powerful regulator of transport 
mechanisms across the cell membrane. Klotho regulates diverse calcium and 
potassium ion channels, as well as several carriers including the Na(+)-coupled 
excitatory amino acid transporters EAAT3 and EAAT4, the Na(+)-coupled phosphate 
cotransporters, NaPi-IIa and NaPi-IIb, and a Na(+)/K(+)-ATPase. All those 
cellular transport regulations contribute in the aging suppressor role of 
Klotho. Future studies will help to determine if the Klotho protein regulates 
cell-surface expression of other transport proteins and is affecting underlying 
mechanisms.