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Part of the skin and hair peptide hub: every topical and cosmetic peptide we cover, with its evidence grade.

Evidence: MediumPeptideResearch ChemicalCosmetic signal peptide (procollagen fragment)Cosmetic ingredient · not a drugWrinkles and photoaged skin

Palmitoyl Pentapeptide-4

The palmitoylated collagen fragment sold as Matrixyl: two small human trials on wrinkles and a laboratory case for how it works

Palmitoyl pentapeptide-4 (pal-KTTKS, sold as Matrixyl) is lysine-threonine-threonine-lysine-serine, a fragment of type I procollagen, with a palmitic acid tail to help it into the skin. It was designed as a topical ingredient to stimulate collagen. In a 12-week split-face trial in 93 women, a moisturiser containing it reduced wrinkles more than the same moisturiser without it; a second trial had 21 participants. It is a cosmetic ingredient, not a medicine.

Overview

What is it?

Palmitoyl pentapeptide-4 is a five-amino-acid fragment of type I procollagen, residues 212 to 216, with palmitic acid attached. The fatty tail matters: in hairless mouse skin, neither the plain peptide nor the palmitoylated one crossed full-thickness skin, but only the palmitoylated form was found in the skin layers, mostly the outermost, and it resisted breakdown by skin enzymes better.

Its human evidence is two trials. In 2005, 93 women aged 35 to 55 used a moisturiser with 3 ppm of the peptide on one side of the face and the same moisturiser without it on the other for 12 weeks; image analysis, expert graders and the women themselves found fewer wrinkles and fine lines on the treated side, and it was well tolerated. A 2023 trial in 21 Indonesian women found it did better than acetyl hexapeptide-3 and placebo on crow's feet over eight weeks, which the authors called an initial study needing larger numbers.

Laboratory and animal work suggests how it might act: at 0.1 µM it halved the conversion of skin fibroblasts into scar-forming myofibroblasts in culture, and in rats a cream or patch containing it improved wound healing. In the US, cosmetic ingredients do not need FDA approval before sale.

Structured data

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.

ClassA lipidated pentapeptide fragment of type I procollagen C-terminal propeptide, used in topical anti-aging formulations to stimulate collagen and fibronectin synthesis.
SequencePal-Lys-Thr-Thr-Lys-Ser
FormulaC39H75N7O10
Molecular weight802.1 g/mol
Half-lifeTopical only; not a systemic drug
Studied dose3 ppm (in the 2005 trial cream) (daily topical application, topical)
US statusResearch Chemical
Evidence levelMedium
Last reviewed2026-10-04

Educational information, not medical advice. The doses on this page come from approved labels, published studies and, where no study exists, amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Evidence

Published Research

These are the studies of palmitoyl pentapeptide-4, read from their PubMed abstracts: two human trials and the laboratory and animal work behind them.

Human2005

Split-face trial in 93 women

In a 12-week, double-blind, placebo-controlled split-face study, a moisturiser with 3 ppm pal-KTTKS significantly reduced wrinkles and fine lines against the same moisturiser alone, by technical and expert-grader image analysis; the peptide was well tolerated and women reported improvement.

PMID: 18492182
Human2023

Crow's feet in 21 Indonesian women

In a double-blind trial of acetyl hexapeptide-3 cream, palmitoyl pentapeptide-4 cream and placebo applied twice daily for eight weeks, the pentapeptide showed better results than the other two on instrument readings, photographs and self-assessment; the authors call for a larger, longer study.

PMID: 36909866
In Vitro2014

Stability and skin penetration

Both KTTKS and pal-KTTKS were rapidly degraded in mouse skin extracts, the palmitoylated form less so. Neither crossed full-thickness hairless mouse skin, but pal-KTTKS was found in the stratum corneum, epidermis and dermis, where plain KTTKS was not detected.

PMID: 25143811
In Vitro2017

Fibroblasts and scar formation

At 0.1 µM, pal-KTTKS halved α-SMA-positive stress fibres in cultured fibroblasts (75% against 38.6%), reducing their transformation into myofibroblasts; the effect was not significant at 0.5 µM.

PMID: 30603464
Animal2022

Wound healing in rats

Over 21 days, patches and creams containing Matrixyl improved wound healing by 63.5% to 81.8% against untreated wounds, and the 1 mg cream and patch outperformed a commercial hydrocolloid dressing.

PMID: 35874243
Safety

Side Effects & Contraindications

Reported Side Effects

From the two human trials.

● Well tolerated by the skin in the 12-week split-face trial
● No safety concerns reported in the 2023 trial abstract

Contraindications & Cautions

A cosmetic ingredient with no drug label. These cautions follow from the evidence.

● Injecting it — it was designed and tested only for use on the skin
● Expecting drug-level effects — the trials measured wrinkles over 8 to 12 weeks
● Tested athletes — see the Sport (WADA) row below
Questions

Frequently Asked Questions

?Is Matrixyl the same as palmitoyl pentapeptide-4?

Yes. Matrixyl is the trade name for palmitoyl pentapeptide-4, also written pal-KTTKS: a five-amino-acid procollagen fragment with a palmitic acid tail.

?Does it reduce wrinkles?

In a 12-week split-face trial in 93 women, a moisturiser containing it reduced wrinkles and fine lines more than the same moisturiser without it; a second trial had 21 participants.

?Does it get into the skin?

In mouse skin it stayed in the skin layers, mostly the outermost, and did not cross full-thickness skin; the palmitic acid tail is what let it enter at all.

Bibliography

References

  1. [pubmed] Robinson LR, et al. "Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin." Int J Cosmet Sci, 2005;27(3):155-60. PMID: 18492182.
  2. [pubmed] Aruan RR, et al. "Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet." J Clin Aesthet Dermatol, 2023;16(2):37-43. PMID: 36909866.
  3. [pubmed] Choi YL, et al. "Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS)." Biomol Ther (Seoul), 2014;22(4):321-7. PMID: 25143811.
  4. [pubmed] Park H, et al. "Effect of Palmitoyl-Pentapeptide (Pal-KTTKS) on Wound Contractile Process in Relation with Connective Tissue Growth Factor and α-Smooth Muscle Actin Expression." Tissue Eng Regen Med, 2017;14(1):73-80. PMID: 30603464.
  5. [pubmed] Kachooeian M, et al. "Matrixyl Patch vs Matrixyl Cream: A Comparative In Vivo Investigation of Matrixyl (MTI) Effect on Wound Healing." ACS Omega, 2022;7(28):24695-24704. PMID: 35874243.
  6. [fda] U.S. Food and Drug Administration. FDA authority over cosmetics: cosmetic products and ingredients, other than color additives, do not need FDA premarket approval. Content current as of November 18, 2025; read September 30, 2026.

Sources & Citations

Every study on this page was read from its PubMed record. Regulatory status comes from FDA's page on its authority over cosmetics, read September 30, 2026. 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.

Last reviewed: 2026-10-04