Follistatin-344

Follistatin-344 is a glycoprotein isoform of follistatin, a protein that binds and neutralizes activin, myostatin and related growth factors. It is a full-size protein of about 344 residues, not a short peptide, and is not approved for any use.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Follistatin is a naturally occurring glycoprotein first identified for its ability to suppress follicle-stimulating hormone secretion from the pituitary. It acts by binding activin and other members of the transforming growth factor β (TGF-β) superfamily, including myostatin, a negative regulator of skeletal muscle growth. The name Follistatin-344 refers to the 344-amino-acid precursor encoded by one of the follistatin gene's alternatively spliced transcripts, which gives rise to the longer circulating isoforms of the protein.

It is important to note that follistatin is a protein, not a short peptide. It is several times larger than most compounds on this site, contains many disulfide bonds and is glycosylated, so it is produced by recombinant expression rather than chemical peptide synthesis. Research on follistatin includes extensive animal work on muscle and reproductive biology, and gene therapy studies delivering the follistatin-344 gene. Recombinant follistatin protein has not been approved for any use.

Structure

The human follistatin gene produces two main transcripts by alternative splicing. One encodes a 344-residue precursor (FST344) and the other a 317-residue precursor (FST317). Removal of a 29-residue signal peptide yields mature proteins of 315 residues (FST315) and 288 residues (FST288); proteolytic processing of FST315 can also produce an intermediate form. The protein contains an N-terminal domain and three follistatin domains rich in cysteine, forming numerous disulfide bonds, and it is N-glycosylated. FST315 has an acidic C-terminal tail that reduces binding to cell-surface heparan sulfate, so it circulates more readily than FST288.

Mechanism

Follistatin binds activins and several other TGF-β superfamily ligands, including myostatin (GDF-8) and some bone morphogenetic proteins, with high affinity. Two follistatin molecules wrap around a ligand dimer, blocking its access to type I and type II receptors. By neutralizing myostatin and activin, which normally restrain muscle growth, follistatin increases muscle mass in animal models when overexpressed.

In the pituitary, neutralization of activin reduces follicle-stimulating hormone secretion, the activity for which follistatin was named. Because its ligands have roles in reproduction, inflammation, wound healing and other processes, systemic follistatin exposure is expected to have broad effects, which are still being characterized.

Research

Muscle growth in animal models

Studies in mice showed that transgenic overexpression of follistatin produces substantial increases in skeletal muscle mass, exceeding the effect of myostatin deletion alone and indicating that follistatin inhibits other muscle-regulating ligands too. Gene delivery of follistatin using adeno-associated virus vectors increased muscle size and strength in mice and in nonhuman primates. This work established follistatin as a major research tool in muscle biology.

Gene therapy in muscular dystrophy

A small phase 1/2a clinical trial delivered the follistatin-344 gene by adeno-associated virus injection into leg muscles of men with Becker muscular dystrophy. Investigators reported on safety and measures of walking distance and muscle histology. This trial tested a gene therapy rather than administration of the protein itself, and its small size and open-label design limit conclusions. Gene therapy approaches have also been studied in other muscle diseases.

Reproductive and other biology

Follistatin is widely studied in reproductive endocrinology for its regulation of follicle-stimulating hormone and its roles in the ovary and placenta. Circulating follistatin levels have been measured in pregnancy, liver disease, metabolic disease and inflammatory conditions. Animal studies have examined its role in wound healing, fibrosis and inflammation. Much of this work measures the endogenous protein rather than administering it.

Evidence quality

The biology of follistatin is well established through decades of laboratory and animal research. Human data on administering follistatin are limited to small gene therapy trials; there are no controlled human studies of recombinant follistatin protein given systemically. Research material labeled follistatin-344 may vary widely in identity and quality. Experimental approaches using follistatin-derived fragments or engineered ligand traps are also under study in muscle and fibrosis research.

Regulatory status

Follistatin is not approved by the FDA for any use, either as a recombinant protein or as a gene therapy, and it is not a recognized substance for US pharmacy compounding. Human studies have been limited to small investigational gene therapy trials. WADA lists follistatin under class S4 as a myostatin-function modifier, prohibited at all times.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

Because follistatin is a recombinant glycoprotein, standard short-peptide analysis is not sufficient. A certificate of analysis should state the expression system and exact construct, since the 344-residue designation refers to the precursor while the secreted mature protein is shorter. Identity should be confirmed by intact mass analysis, which will be broadened by glycosylation, and by peptide mapping or sequencing. SDS-PAGE and size-exclusion chromatography should show purity and absence of aggregates. Correct disulfide formation and biological activity, such as activin-binding or neutralization assays, are key quality indicators. Endotoxin testing is important for proteins expressed in bacteria. The site's computed mass from sequence does not account for glycans.

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Recombinant follistatin is typically supplied lyophilized, often with carrier protein or stabilizing excipients, and should be stored at -20 °C to -80 °C as specified by the manufacturer. Reconstituted protein is prone to aggregation and adsorption to surfaces, so it should be dissolved gently without vortexing, often in buffer with carrier protein for lab use, aliquoted, stored frozen, and protected from repeated freeze-thaw cycles. Stability depends strongly on formulation, so manufacturer data should take precedence.

Download the Follistatin-344 data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• PEG-MGF

  PEG-MGF is a PEGylated synthetic peptide based on the E-peptide of mechano growth factor, a splice variant of insulin-like growth factor 1. The PEGylated form itself has little published characterization and no human evidence.

• IGF-1 LR3

  IGF-1 LR3 is a recombinant analogue of insulin-like growth factor 1 with an arginine substitution at position 3 and a 13-residue N-terminal extension. It binds IGF-binding proteins weakly and is widely used in cell culture.

• Tesamorelin

  Tesamorelin is a stabilized synthetic analogue of human growth hormone releasing hormone. It is FDA-approved as Egrifta for reducing excess abdominal fat in adults with HIV-associated lipodystrophy.

References

1. Lee SJ, McPherron AC Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci U S A. 2001. Find on PubMed
2. Mendell JR, Sahenk Z, Malik V, et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Mol Ther. 2015. Find on PubMed
3. PubMed: all indexed literature on Follistatin-344
4. ClinicalTrials.gov: registered studies mentioning Follistatin-344