Palmitoyl Pentapeptide-4
Matrixyl (Palmitoyl Pentapeptide-4) — evidence, uses & the "collagen boosting" claim

Class: peptide
INCI name: Palmitoyl Pentapeptide-4
Synonyms: Matrixyl® (trade name, Sederma / Croda)
INCI: Palmitoyl Pentapeptide-4
Pal-KTTKS
Palmitoyl Oligopeptide (older INCI, Matrixyl-family peptides)
formerly "Palmitoyl Pentapeptide-3" (pre-2006)
Palmitoyl-Lys-Thr-Thr-Lys-Ser
Trade names: Matrixyl
Function tags: skin appearance (cosmetic)
fine lines & wrinkles
(reference:) collagen/ECM signalling
Overall evidence grade: B
WADA prohibited: no
Last updated: 2026-07-20

In brief: Matrixyl (INCI Palmitoyl Pentapeptide-4) is a synthetic signal peptide — a palmitoylated fragment (Pal-KTTKS) of type I procollagen — used in anti-ageing cosmetics. It has the most-replicated clinical evidence among cosmetic signal peptides, anchored by a 12-week split-face RCT, showing a modest improvement in the appearance of photoaged skin. Many of the larger figures quoted for it (e.g. "+117% collagen") come from in-vitro or manufacturer data, not the controlled human trial.

## Identity a synthetic **lipopeptide** — the pentapeptide **KTTKS** (5 amino acids, < 40 aa → peptide), a matrikine fragment of the C-terminal propeptide of **type I procollagen**, conjugated to **palmitic acid** (C16) to aid skin penetration (unmodified KTTKS is hydrophilic, ~562 Da, and penetrates poorly). KTTKS identified 1993 (Katayama); Matrixyl launched 2000 by Sederma. ## Development & history - The active **KTTKS** sequence was identified in **1993 (Katayama et al.)** as a collagen-propeptide fragment that stimulates matrix synthesis. To make it usable on skin, the French active-ingredient house **Sederma** attached a palmitoyl tail and launched **Pal-KTTKS as Matrixyl in 2000** — described as the first peptide active designed for anti-ageing cosmetics (Lintner & Peschard, 2000).
- The line then expanded commercially: **Matrixyl → Matrixyl 3000** (a two-peptide system) **→ Matrixyl Synthe'6**. Sederma is part of **Croda**. Like Argireline, it has only ever been a cosmetic ingredient, not a drug. ## Variants - **Matrixyl** = single peptide **Pal-KTTKS** (Palmitoyl Pentapeptide-4).
- **Matrixyl 3000** = two-component: **Palmitoyl Tripeptide-1 (Pal-GHK)** (sometimes listed under the older INCI name **Palmitoyl Oligopeptide**) + **Palmitoyl Tetrapeptide-7 (Pal-GQPR)** — different signals (collagen + IL-6 downregulation).
- **Matrixyl Synthe'6** = Palmitoyl Tripeptide-38. ## Mechanism (as proposed) KTTKS is a **matrikine** — a fragment released during type I collagen processing that acts as a feedback signal. Matrixyl is proposed to mimic this signal: once the palmitoyl tail carries it into the dermis, KTTKS is proposed to bind fibroblast surface receptors (TGF-β-linked signalling) and stimulate extracellular-matrix synthesis (collagen, fibronectin, HA), with the effect described as self-limiting. Much of this is characterised in vitro; the extent and consistency of the effect on intact human skin is more modest than the cell-culture figures suggest.

## Related reading

The anti-inflammatory side of the Matrixyl 3000 blend — its Palmitoyl Tetrapeptide-7 component and its "inflammaging" role — sits alongside the other soothing peptides in our [anti-inflammatory peptides reference list](/learn/anti-inflammatory-peptides). For how signal peptides like Matrixyl fit into a routine — layering, timing, and spotting a well-formulated product — see [how to use peptides](/learn/how-to-use-peptides). For where Matrixyl ranks among the cosmetic peptides by evidence, see [cosmetic peptides ranked by evidence](/learn/best-peptides-for-skin) and the dedicated [Matrixyl explainer](/learn/matrixyl-explained).

Evidence grades by outcome:
outcome: Topical: appearance of photoaged skin (fine lines, wrinkle depth, roughness)
grade: B
base: Robinson 2005 — 12-week split-face, double-blind, vehicle-controlled RCT, n=93
effect: Statistically significant improvement vs placebo
caveat: Best-evidenced cosmetic peptide of this set, but effect is modest; single main RCT; small
outcome: ECM synthesis in vitro (collagen I/III, fibronectin, HA; MMP-1↓, TIMP-1↑)
grade: B
base: Fibroblast assays at ~3 ppm
effect: Substantial stimulation
caveat: In vitro; the eye-catching "+117%/+327%" figures are cell-culture, not human outcomes
outcome: Comparable to retinol
grade: C
base: Some measures vs low-dose retinol (~0.07%)
effect: Comparable on select endpoints, far gentler
caveat: Not equivalent to prescription retinoids; comparison is to low-concentration retinol
outcome: Skin penetration at cosmetic doses
base: Efficacy seen at 3–5 ppm; formal dose-escalation not published
effect: Palmitoyl tail improves penetration
caveat: Better than plain KTTKS, but a formal 1–50 ppm dose study is lacking
outcome: "Collagen-boosting" collagen synthesis in human skin
grade: D
base: Marketing claim
caveat: The 12-week vehicle-controlled human trial measured appearance — fine lines, wrinkle depth, roughness — not collagen synthesis in skin; the collagen mechanism itself rests on fibroblast culture
outcome: "+117% collagen" the quoted magnitude
grade: D
base: Marketing claim
caveat: The +117% figure is a fibroblast cell-culture readout, not a human result. The human data is a single unreplicated manufacturer-run biopsy study showing raised collagen and elastin markers over about four months of twice-daily use — the right direction, well short of the quoted magnitude
outcome: Safety (topical)
base: Broad cosmetic use
effect: Well tolerated; no photosensitivity
caveat: Non-irritating; suitable for sensitive skin

Legal status:
region: EU
status: Lawful cosmetic
note: a lawful cosmetic ingredient (EU Regulation (EC) 1223/2009; US cosmetic law), sold over-the-counter worldwide. No injectable or "research" lane, no drug filing. Straightforwardly sellable as a cosmetic — the constraint is the claims.

Cosmetic claims:
allowed: for the **appearance** of firmer, plumper, smoother skin
helps reduce the **look** of fine lines and wrinkles
supports a more youthful-looking complexion
forbidden: boosts / stimulates / increases **collagen** (synthesis/production)
collagen-boosting
rebuilds collagen
by function
wound healing
repairs
regenerates
the proposed mechanism

Note: Cosmetic signal peptide — a different archetype from Argireline. Argireline is a neuromodulator (proposed to relax muscle); Matrixyl is a matrikine / signal peptide (proposed to tell skin to build matrix). It is the best-evidenced of the common cosmetic peptides — and its whole marketing ("collagen-boosting") is the claim trap.

Sources:
Robinson LR, Fitzgerald NC, Doughty DG, et al. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. Int J Cosmet Sci. 2005. (anchor RCT, n=93)
Lintner K, Peschard O. Biologically active peptides: from a laboratory bench curiosity to a functional skin care product. Int J Cosmet Sci. 2000. (Sederma origin)
Katayama K, et al. (Identification of the KTTKS collagen-stimulating sequence.) 1993.
Jones RR, et al. Collagen-stimulating effect of peptide amphiphile C16-KTTKS on human fibroblasts. Mol Pharm. 2013. (PMID 23320752)
He, Wang, Qu. (Peptide–cell-surface interactions in cosmetic peptides — review.) Front Pharmacol. 2023.