Klotho Research Peptide Pen (20 mcg)

What alpha-Klotho is. Human Klotho (UniProt Q9UEF7) is a 1012-residue single-pass membrane protein with a calculated, unglycosylated mass of 116181 Da. Its extracellular region holds two glycosyl hydrolase-like domains, KL1 (residues 57-506) and KL2 (residues 515-953), followed by a transmembrane segment and a short cytoplasmic tail. The klotho gene was first described in mice in 1997 as encoding a membrane protein that shares sequence similarity with beta-glucosidase enzymes. The extracellular domain can be shed from the membrane, and a structural study describes this shed alpha-Klotho as a non-enzymatic scaffold.

The construct. The product is a long-release alpha-Klotho construct. According to the supplier it is a soluble alpha-Klotho protein joined through a glycine-serine linker to a C-terminal albumin-binding tail (GGSGGSGGSGGRLIEDICLPRWGCLWEDD). The tail contains the SA21-type peptide RLIEDICLPRWGCLWEDD, an albumin-binding sequence described in 2002 for lengthening the half-life of proteins in animals. The exact boundaries and mass of the construct are not disclosed. It is not KP1 and not a short Klotho-derived fragment.

Supplier claim. The supplier states a long-release profile of up to 19 days. This is a supplier claim: no independent pharmacokinetic data are cited here.

Dosing note. No human dosing data exist for this product. The schedule shown in the dosage section is a conservative house research protocol built on the claimed long-release profile and the 20 mcg pen, and it is not a literature dose.

Storage and handling. Keep the pen as stated on its label and in the accompanying documentation and avoid repeated temperature cycling. For laboratory research use only.

FGF23 co-receptor. In 2006 it was reported that Klotho binds FGF23 and enables high-affinity binding of FGF23 to the cell surface. Klotho alone appeared unable to signal inside the cell, and together with FGFR1(IIIc) it reconstituted the FGF23 receptor. In 2018 a structure of a 1:1:1 complex of the shed extracellular domain of alpha-Klotho, the FGFR1c ligand-binding domain and FGF23 was published. In it alpha-Klotho tethers FGFR1c through its D3 domain and FGF23 through its C-terminal tail, and its structure is incompatible with a glycosidase activity.

Insulin and IGF1 signalling. In a 2005 mouse study Klotho was described as a circulating hormone that binds a cell-surface receptor and represses intracellular insulin and IGF1 signals.

Albumin binding. Peptides with the core sequence DICLPRWGCLW bind serum albumin of several species. A related sequence fused to a Fab fragment reduced its clearance in mice and rabbits and extended its half-life. The tail of this construct is of the SA21 type; whether it behaves the same way in the full construct is a supplier claim.

• Two-Domain Structure:
  Full-length human alpha-Klotho (UniProt Q9UEF7) is annotated as a 1012-residue single-pass membrane protein. Its extracellular region holds two glycosyl hydrolase-like domains, KL1 (residues 57-506) and KL2 (residues 515-953), followed by a transmembrane segment and a short cytoplasmic tail. The klotho gene was first described in mice in 1997 as encoding a membrane protein with sequence similarity to beta-glucosidase enzymes.
• FGF23 Co-Receptor:
  In cell models, Klotho bound FGF23 and enabled high-affinity binding of FGF23 to the cell surface. Klotho alone appeared unable to signal inside the cell, and together with FGFR1(IIIc) it reconstituted the FGF23 receptor. In wild-type mice, an anti-Klotho monoclonal antibody induced FGF23 incompetence. This makes Klotho a useful tool for studying FGF23 signalling in research models.
• Shed Scaffold Form:
  A published atomic structure describes a 1:1:1 complex of the shed extracellular domain of alpha-Klotho, the FGFR1c ligand-binding domain and FGF23. In this complex alpha-Klotho tethers FGFR1c through its D3 domain and FGF23 through its C-terminal tail, while heparan sulfate remains a cofactor. The authors concluded that shed alpha-Klotho is a non-enzymatic scaffold, not a glycosidase.
• Mouse Ageing Models:
  In a 1997 mouse study, a defect in klotho gene expression produced a syndrome that resembles human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. The authors suggested that the klotho gene product may function in a signalling pathway that regulates ageing in vivo. This is animal data only and does not describe this product.
• Insulin and IGF1 Signalling:
  A 2005 mouse study reported that overexpression of Klotho extended life span. Klotho was described as a circulating hormone that binds a cell-surface receptor and represses intracellular insulin and IGF1 signals, and ageing-like phenotypes of Klotho-deficient mice were alleviated by perturbing insulin and IGF1 signalling. These are mouse findings only, and no human outcome is implied.
• Albumin-Binding Tail:
  This construct carries a C-terminal tail (GGSGGSGGSGGRLIEDICLPRWGCLWEDD) containing the SA21-type albumin-binding peptide RLIEDICLPRWGCLWEDD. In a 2002 animal study, peptides with the core sequence DICLPRWGCLW bound serum albumin of several species, and a related sequence fused to a Fab fragment extended its half-life 37-fold in rabbits and 26-fold in mice. Those data concern a Fab fragment, not this construct.
• Long-Release Claim:
  The supplier states that the construct has a long-release profile of up to 19 days. This is a supplier claim. No independent pharmacokinetic data are cited here, and the pen schedule is a house research protocol, not a literature dose.
• Reference Protein Entry:
  UniProt lists human alpha-Klotho under accession Q9UEF7, with a calculated, unglycosylated mass of 116181 Da for the full-length precursor. The exact mass and boundaries of the product construct are not disclosed. It is not KP1 and not a short Klotho-derived fragment, so the identity data refer to the parent protein.

• Kuro-o M et al. Nature 1997 Mouse genetics
• Kurosu H et al. Science 2005 Mouse study
• Urakawa I et al. Nature 2006 Cell and mouse study
• Chen G et al. Nature 2018 Structural study
• Dennis MS et al. J Biol Chem 2002 Albumin-binding peptides
• UniProtKB Q9UEF7 (KLOTH_HUMAN) Registry

Low-dose research protocol

• Dose: 1 mcg (5 clicks)
• Duration: 40 weeks (one pen = 20 doses)
• Frequency: One dose every 14 days, subcutaneous (SubQ) with the pen
• Cycle Interval: Pause of at least 4 weeks before a repeat course
• Pen Coverage: 1 pen = 20 doses (one dose every 14 days)
• Goal / Description: Conservative entry dose of 5 clicks (1.0 mcg), kept constant. No human dosing data exist for this product. The schedule is a conservative house research protocol based on the claimed long-release profile (up to 19 days per the supplier) and the 20 mcg pen; it is not a literature dose.

Titration research protocol

• Dose: 1 - 2 mcg (5 - 10 clicks)
• Duration: 5 clicks (1.0 mcg) for the first 4 doses, then 10 clicks (2.0 mcg)
• Frequency: One dose every 14 days, subcutaneous (SubQ) with the pen
• Cycle Interval: Pause of at least 4 weeks before a repeat course
• Pen Coverage: 1 pen = 20 - 10 doses (one dose every 14 days)
• Goal / Description: Gradual step from 1.0 mcg to 2.0 mcg; one pen = 20 doses at 5 clicks or 10 doses at 10 clicks. No human dosing data exist for this product. The schedule is a conservative house research protocol based on the claimed long-release profile (up to 19 days per the supplier) and the 20 mcg pen; it is not a literature dose.

Standard research protocol

• Dose: 2 mcg (10 clicks)
• Duration: 20 weeks (one pen = 10 doses)
• Frequency: One dose every 14 days, subcutaneous (SubQ) with the pen
• Cycle Interval: Pause of at least 4 weeks before a repeat course
• Pen Coverage: 1 pen = 10 doses (one dose every 14 days)
• Goal / Description: Upper house dose of 10 clicks (2.0 mcg), kept constant. No human dosing data exist for this product. The schedule is a conservative house research protocol based on the claimed long-release profile (up to 19 days per the supplier) and the 20 mcg pen; it is not a literature dose.

No stack is offered for Klotho in this catalogue:

• Klotho alone: the cited studies evaluated Klotho on its own, in cell and mouse models.
• Combination designs: no validated combination partner is offered here.

Note: any combination is for experimental design only and is not safety or efficacy guidance.

Klotho in this form is a research material. No human safety data exist for this construct, and none of the cited papers reports human exposure to it.

For research context:

• The cited findings come from cell models, structural work and mouse studies.
• The albumin-binding tail comes from a 2002 animal study of a Fab fragment, not from this construct.
• Handle only under laboratory research conditions. Not for human or veterinary use.

• CAS #: N/A
• Molecular Formula: N/A
• Sequence (AA): N/A
• Molecular Weight: 116181 Da (calculated, unglycosylated, full-length precursor)
• PubChem CID: N/A
• Half-Life: Claimed long-release profile, up to 19 days per the supplier; no independent pharmacokinetic data
• Synonyms: alpha-Klotho, Klotho, KL, KLOTH_HUMAN
• Type: Recombinant research protein (alpha-Klotho, long-release construct)
• Research Focus: Anti-ageing membrane protein and co-receptor of FGF23/FGFR1c; studied in mouse ageing models and FGF23 signalling
• C-terminal albumin-binding tail: GGSGGSGGSGGRLIEDICLPRWGCLWEDD