Quick Answer
KP1 (Klotho-derived peptide 1) is a 30-amino-acid peptide taken from the human Klotho protein. Since 2022, five cell and mouse studies from the group that discovered it have reported that it blocks TGF-beta receptor 2 and reduces fibrosis and injury in mouse kidneys and livers. It has never been tested in people. The well-known Klotho findings on lifespan and memory come from the full protein, not from KP1.
Key facts
- Compound type: synthetic 30-amino-acid peptide, residues 57 to 86 of human alpha-Klotho.
- Reported target: TGF-beta receptor 2 (TβR2); in acute kidney injury, also the mitochondrial protein ATAD3A.
- First described: 2022, Nature Communications.
- Evidence: cell culture and mouse studies only, all from one research group.
- Human trials of KP1 (October 2026): none registered.
- Status: research compound; not a medicine anywhere.
Klotho has one of the best stories in ageing biology: a gene whose loss makes mice age early and whose excess makes them live longer. KP1 borrows the name. It is a small, practical piece of the protein, chosen for a single action, and its own evidence is much narrower than the Klotho headlines suggest. This article separates the two.
What is Klotho?
The gene was described in 1997, when mice with a defective copy developed a syndrome resembling human ageing: a short lifespan, arteriosclerosis, skin atrophy, osteoporosis and emphysema (Kuro-o et al., 1997). In 2005 the same field showed the reverse: mice engineered to make extra Klotho lived longer, and the protein circulated as a hormone that dampened insulin and IGF-1 signalling (Kurosu et al., 2005).
Klotho's best-understood job is in mineral balance. In the kidney, membrane-bound alpha-Klotho joins FGF receptors to form the receptor for FGF23, a bone-derived hormone that controls phosphate (Urakawa et al., 2006). A soluble form is shed into the blood. A related protein, beta-Klotho, plays the same co-receptor role for FGF21; our article on FGF21 covers it.
What is KP1 and how was it found?
The full Klotho protein is large and complex, which makes it hard to produce and use. In 2022 a team screened a series of peptides taken from the human Klotho sequence for one property: stopping kidney fibroblasts from turning into scar-forming cells when exposed to TGF-beta. One peptide, residues 57 to 86 near the start of the protein, did. They called it KP1 (Yuan et al., 2022).
KP1 bound TGF-beta receptor 2 and prevented TGF-beta from binding it, which blocked the downstream Smad2/3 and MAP kinase signals. In mouse models of kidney fibrosis, including unilateral ureteral obstruction, KP1 injected into a vein accumulated preferentially in injured kidneys, preserved kidney function, reduced fibrosis and restored the kidneys' own Klotho production. The authors noted that the KP1 sequence is highly conserved across species, from humans to fruit flies.
What has KP1 done in later studies?
- Senescence in fibrotic kidneys (2024). In mouse chronic kidney disease, KP1 lowered the senescence markers p21, p16 and γ-H2AX in tubule cells. The authors traced this to restored Klotho: a microRNA, miR-223-3p, blocks Klotho production, and KP1 counteracted it (Zhang et al., 2024).
- COVID-19-associated kidney injury (2024). Klotho-deficient mice were more susceptible to kidney injury after expression of the SARS-CoV-2 N protein; KP1 reduced tubular injury in cultured cells and in a mouse ischaemia model (Xu et al., 2024).
- Liver fibrosis (2026). KP1 blocked TGF-beta activation of hepatic stellate cells, the liver's scar-forming cells, and reduced fibrosis in Klotho-deficient mice and in a chemical and a surgical mouse model of liver injury (Tan et al., 2026).
- Acute kidney injury (2026). In cisplatin and ischaemia-reperfusion mouse models, KP1 entered tubule cells, bound the mitochondrial protein ATAD3A, prevented its breakdown and limited cytochrome c release and cell death (Zhang et al., 2026). This is a second proposed mechanism, separate from TGF-beta receptor blocking.
The same group also described KP6, a different Klotho-derived peptide that binds Wnt proteins and reduced kidney damage in diabetic mice without changing blood phosphate or calcium (Chen et al., 2022). Every KP1 and KP6 study cited here shares the same senior author. That is normal for a new compound, but it means no independent laboratory has yet reproduced the results.
Where do the lifespan and memory claims come from?
Not from KP1. The results usually quoted for Klotho involve the full protein or a different fragment:
- Lifespan: mice genetically engineered to overproduce Klotho throughout life (Kurosu et al., 2005).
- Cognition in mice: people carrying one copy of a gene variant called KL-VS had higher Klotho levels and better cognitive scores, and mice overproducing Klotho performed better on learning and memory tests (Dubal et al., 2014). A separate Klotho fragment, αKL-F, improved cognition in mice when injected, even though it did not cross into the brain (Leon et al., 2017).
- Monkeys: a single low dose of the rhesus Klotho protein improved memory in aged rhesus monkeys, while a high dose did not (Castner et al., 2023).
None of these studies used KP1, and KP1 has not been tested for memory, cognition or lifespan.
Has Klotho been tested in humans?
Barely. As of 30 October 2026, ClinicalTrials.gov lists no trial of KP1. It lists three small studies that try to raise Klotho itself:
- A pilot of injectable Klotho plasmid gene therapy in 14 healthy adults, with no placebo group (NCT07216781, active, not recruiting).
- A pilot combining Klotho and follistatin gene therapy in 14 healthy adults, with no placebo group (NCT07285629, completed in April 2026, no results posted).
- A placebo-controlled phase 1b study of Klotho mRNA given into a vein, in about 21 people (NCT07544420, not yet recruiting).
The two gene therapy pilots measure blood Klotho levels and side effects. Small open-label studies like these can show whether Klotho levels rise, but not whether anything clinical changes.
What is not known yet?
- Independent replication. Every published KP1 result comes from one research group.
- Humans. There are no human data on KP1 at all: no safety, no pharmacokinetics, no efficacy.
- Stability and exposure. The studies reviewed here do not report a half-life for KP1 in the body.
- Beyond the kidney and liver. KP1 has not been studied in the brain, heart, muscle or for lifespan.
- Which mechanism matters. TGF-beta receptor blocking, restored Klotho production and the mitochondrial ATAD3A effect have each been reported; how they relate is not settled.
The bottom line
KP1 is a well-designed piece of the Klotho protein that blocks TGF-beta receptor 2 and has reduced fibrosis and injury in mouse kidneys and livers in five studies from one group. It is not the Klotho of the lifespan and memory headlines, and it has never been given to people. Its standing depends on whether other laboratories reproduce the results. As of October 2026 it is a research compound only. The Klotho (KP1) profile has the register details.
References
- Castner SA, et al. (2023). Longevity factor klotho enhances cognition in aged nonhuman primates. Nature Aging. PubMed 37400721
- Chen X, et al. (2022). Klotho-derived peptide 6 ameliorates diabetic kidney disease by targeting Wnt/β-catenin signaling. Kidney International. PubMed 35644285
- Dubal DB, et al. (2014). Life extension factor klotho enhances cognition. Cell Reports. PubMed 24813892
- Kuro-o M, et al. (1997). Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. PubMed 9363890
- Kurosu H, et al. (2005). Suppression of aging in mice by the hormone Klotho. Science. PubMed 16123266
- Leon J, et al. (2017). Peripheral Elevation of a Klotho Fragment Enhances Brain Function and Resilience in Young, Aging, and α-Synuclein Transgenic Mice. Cell Reports. PubMed 28793260
- Tan H, et al. (2026). Klotho-derived peptide 1 ameliorates hepatic fibrosis induced by αKlotho deficiency and liver injury. International Journal of Biological Sciences. PubMed 41608630
- Urakawa I, et al. (2006). Klotho converts canonical FGF receptor into a specific receptor for FGF23. Nature. PubMed 17086194
- Xu J, et al. (2024). Klotho-derived peptide KP1 ameliorates SARS-CoV-2-associated acute kidney injury. Frontiers in Pharmacology. PubMed 38239193
- Yuan Q, et al. (2022). A Klotho-derived peptide protects against kidney fibrosis by targeting TGF-β signaling. Nature Communications. PubMed 35064106
- Zhang X, et al. (2024). Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation. Theranostics. PubMed 38164143
- Zhang X, et al. (2026). Klotho-Derived Peptide 1 Protects against Acute Kidney Injury by Directly Targeting Mitochondrial ATAD3A. Advanced Science. PubMed 42640132
- ClinicalTrials.gov. Studies with Klotho as an intervention, records read 30 October 2026. ClinicalTrials.gov search