Part of the skin and hair peptide hub: every topical and cosmetic peptide we cover, with its evidence grade.
Tetrapeptide-21
Gly-Glu-Lys-Gly, a collagen-stimulating cosmetic peptide with one small placebo-controlled skin study and a literature mostly about getting it into skin
Tetrapeptide-21 is the cosmetic ingredient name for GEKG, four amino acids designed in 2011 from sequences in the skin's own matrix proteins. In cultured skin cells it raised collagen production, and in a small double-blind study published as a letter it reduced skin roughness where a placebo cream did not. Since then the research has been about delivery: GEKG is small but highly water-loving, so little of it crosses the skin barrier from an ordinary cream.
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What is it?
Many anti-wrinkle peptides rest on the matrikine idea: when the skin's collagen and other matrix proteins are broken down, some of the small fragments signal fibroblasts to make more matrix, so applying such a fragment might prompt repair. The founding GEKG paper names the pentapeptide KTTKS as the classic example. GEKG came out of the same line of thinking by a different route: its developers searched matrix-protein sequences by computer and designed the tetrapeptide from them, then tested it.
Their 2011 report, a short letter in Experimental Dermatology, made three claims. In human dermal fibroblasts, GEKG significantly increased collagen at both the protein and the messenger-RNA level. In a double-blind, randomised, placebo-controlled study of 10 volunteers with an average age of 48 it raised collagen in the skin. And in 30 volunteers whose facial wrinkles were measured by fringe projection, a three-dimensional surface scan, skin roughness fell significantly with GEKG and not with placebo. The abstract gives no concentration, no treatment length and no size of the effect, and no independent group has repeated the human work.
Everything published since concerns delivery or cells. A 2018 study put GEKG into creams and a water-in-oil microemulsion and measured how much entered excised human skin over five hours; the microemulsion carried it into the deeper living layers and through the skin significantly better than a standard cream, and adding a penetration enhancer to an ordinary emulsion helped only a little. A 2026 study loaded it into self-assembling elastin-peptide gels, which slowed its passage through skin over 72 hours, and a 2025 cell study found it raised fibroblast survival and matrix genes, more so when combined with injectable platelet-rich fibrin. A 2022 review of anti-wrinkle peptides used GEKG as one example of a general problem: cell studies show effects, but most such peptides do not reach their targets in the skin in useful amounts without help.
For a buyer, tetrapeptide-21 is a cream ingredient with a plausible cell effect and one small, unreplicated human study. It is not a drug, it is not injected, and a product label stating that it contains the peptide says nothing about how much reaches living skin, which depends on the formulation.
At a Glance
Every value in this table is printed from the Grey Peptides dataset, the same record the compound explorer and comparison tool read, so the three can never disagree.
Published Research
These are the studies of tetrapeptide-21 read from their PubMed abstracts on October 29, 2026: one small human study, two delivery studies using excised human skin, one fibroblast study and one review. The review is carded because its abstract names GEKG among the peptides it assessed.
Collagen and wrinkles: the founding study
Designed by computer from matrix-protein sequences, GEKG raised collagen protein and mRNA in human dermal fibroblasts. A double-blind, randomised, placebo-controlled study of 10 volunteers (mean age 48.2) showed more collagen in the skin, and in 30 volunteers measured by fringe projection only GEKG, not placebo, significantly reduced skin roughness.
Getting GEKG into excised human skin
Formulations containing 5,000 ppm GEKG were applied to excised human skin for 30, 100 and 300 minutes. A water-in-oil microemulsion moved it into the deeper living layers and through the skin significantly better than a standard cream; at 50 ppm, emulsions with glyceryl caprylate/caprate as enhancer showed only a trend towards better penetration.
Elastin-peptide gels for slow release
Self-assembling elastin-derived peptide hydrogels loaded with tetrapeptide-21 slowed its passage through skin: 7.5% to 20.9% permeated over 72 hours, against 26.6% from a plain solution, with the second-generation gel releasing it most slowly.
Fibroblasts with platelet-rich fibrin
In human dermal fibroblasts, GEKG alone and especially combined with injectable platelet-rich fibrin raised cell viability and the expression of COL1A1, FN1 and HAS1 at 72 hours, more than either treatment alone.
Skin permeability of anti-wrinkle peptides
Reviews why anti-wrinkle peptides, GEKG among them, penetrate skin poorly, and the chemical, physical and carrier methods tried to fix it; it concludes that cell-study efficacy is of little use unless enough peptide reaches its target, which most do not without enhancement.
Side Effects & Contraindications
Reported Side Effects
From the abstracts read.
Contraindications & Cautions
A cosmetic ingredient, not a medicine, so there is no label.
Legal Status
A cosmetic ingredient, not a drug.
Frequently Asked Questions
?What is tetrapeptide-21?
The cosmetic ingredient name for GEKG (glycine, glutamic acid, lysine, glycine), a four-amino-acid peptide designed to stimulate collagen production in skin.
?Does it reduce wrinkles?
One small double-blind study in 2011 found it reduced skin roughness where a placebo did not, in 30 volunteers. The abstract gives no concentration or effect size, and no independent study has repeated it.
?Does it get into the skin?
Not easily. It is very water-loving, and studies on excised human skin found a microemulsion delivered it far better than a standard cream. How much reaches living skin depends on the product's formulation.
?What concentration is used?
No human study states one. A laboratory delivery study used test formulations with 50 ppm and 5,000 ppm (0.005% and 0.5%) on excised skin; these were chosen to measure penetration, not effect.
References
- [other] PubChem CID 42630677, GEKG peptide: formula C15H27N5O7, molecular weight 389.40. Read October 28, 2026. https://pubchem.ncbi.nlm.nih.gov/compound/42630677
- [clinical-trial] Farwick M, et al. "Bioactive tetrapeptide GEKG boosts extracellular matrix formation: in vitro and in vivo molecular and clinical proof." Exp Dermatol, 2011;20(7):602-4. PMID: 21692860.
- [pubmed] Sommer E, et al. "Dermal peptide delivery using enhancer molecules and colloidal carrier systems. Part III: Tetrapeptide GEKG." Eur J Pharm Sci, 2018;124:137-144. PMID: 30165235.
- [pubmed] Stephenson H, et al. "Elastin-derived peptide hydrogels for sustained dermal delivery of tetrapeptide-21." Int J Pharm, 2026;689:126490. PMID: 41421628.
- [pubmed] Paccola AGL, et al. "Synergistic Effects of Injectable Platelet-Rich Fibrin and Bioactive Peptides on Dermal Fibroblast Viability and Extracellular Matrix Gene Expression: An In Vitro Study." Molecules, 2025;30(16). PMID: 40871567.
- [review] Mortazavi SM, et al. "Skin permeability, a dismissed necessity for anti-wrinkle peptide performance." Int J Cosmet Sci, 2022;44(2):232-248. PMID: 35302659.
- [pubmed] Park J, et al. "D-tyrosine adds an anti-melanogenic effect to cosmetic peptides." Sci Rep, 2020;10(1):262. PMID: 31937863.
Sources & Citations
Every study on this page was read from its PubMed record on October 29, 2026. Concentrations are printed only where a study used them; no supplier's figure is used. A study of a D-tyrosine-modified GEKG is listed under References with a reason. Grey Peptides sells nothing and links to no vendor.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Consult a licensed healthcare provider before making health decisions.