The α-Klotho protein is an obligate coreceptor for fibroblast growth factor 23 (FGF23) and plays a critical role in aging and age-related diseases. It is produced in the kidneys, brain, and other tissues and is associated with chronic inflammatory conditions such as atherosclerosis, diabetes, and Alzheimer's disease. Klotho exists in membrane and soluble forms (s-Klotho), with s-Klotho having endocrine properties and acting as a coreceptor for FGF23. It inhibits NF-κB and the NLRP3 inflammasome, which are key pathways in inflammation and aging. s-Klotho also blocks the TGF-β receptor and Wnt ligands, reducing fibrosis and protecting against muscle atrophy. Klotho deficiency is linked to various inflammatory and degenerative diseases, including those affecting the kidneys, cardiovascular system, and brain. Klotho inhibits NF-κB activation, reduces oxidative stress, and mitigates inflammation, which is central to the aging process (inflammaging). It also protects against cell death and tissue damage by counteracting inflammatory signals. Klotho's anti-inflammatory and anti-fibrotic effects are mediated through multiple pathways, including the inhibition of the NLRP3 inflammasome, reduction of ER stress, and activation of antioxidant pathways such as Nrf2 and FoxO. Klotho has therapeutic potential in various diseases, including diabetes, atherosclerosis, and neurodegenerative disorders like Alzheimer's disease. Its role in protecting against inflammation, fibrosis, and aging-related pathologies makes it a promising target for therapeutic intervention.The α-Klotho protein is an obligate coreceptor for fibroblast growth factor 23 (FGF23) and plays a critical role in aging and age-related diseases. It is produced in the kidneys, brain, and other tissues and is associated with chronic inflammatory conditions such as atherosclerosis, diabetes, and Alzheimer's disease. Klotho exists in membrane and soluble forms (s-Klotho), with s-Klotho having endocrine properties and acting as a coreceptor for FGF23. It inhibits NF-κB and the NLRP3 inflammasome, which are key pathways in inflammation and aging. s-Klotho also blocks the TGF-β receptor and Wnt ligands, reducing fibrosis and protecting against muscle atrophy. Klotho deficiency is linked to various inflammatory and degenerative diseases, including those affecting the kidneys, cardiovascular system, and brain. Klotho inhibits NF-κB activation, reduces oxidative stress, and mitigates inflammation, which is central to the aging process (inflammaging). It also protects against cell death and tissue damage by counteracting inflammatory signals. Klotho's anti-inflammatory and anti-fibrotic effects are mediated through multiple pathways, including the inhibition of the NLRP3 inflammasome, reduction of ER stress, and activation of antioxidant pathways such as Nrf2 and FoxO. Klotho has therapeutic potential in various diseases, including diabetes, atherosclerosis, and neurodegenerative disorders like Alzheimer's disease. Its role in protecting against inflammation, fibrosis, and aging-related pathologies makes it a promising target for therapeutic intervention.