Follistatin-315

Follistatin exists in three principal isoforms. FST-288 carries a heparin-binding domain that anchors it to cell-surface proteoglycans, making it act locally and potently at the tissue where it is produced. FST-315 lacks that anchoring behaviour, stays in circulation and is the isoform that accounts for most measurable serum follistatin. FST-344 is simply FST-315 with its signal peptide still attached, so the two products sold under those names converge to the same molecule once injected. Ligand binding is identical - myostatin, activin A and B, and GDF-11 are all sequestered, blocking Smad2/3 signalling through activin type II receptors.

Targets: Myostatin (GDF-8), Activin A, Activin B, GDF-11

• · The protocol is copied wholesale from FST-344 folklore. There is no independent evidence for either.

Work out your exact syringe units →

• very commonCounterfeit or inactive product— Same manufacturing-cost problem as FST-344.
• commonInjection-site reaction
• uncommonOff-target activin blockade— Systemic distribution is precisely the point of this isoform, so off-target effects on FSH, inflammation and reproduction are more likely, not less.
• rareTheoretical tumour-growth risk— Blocking a tumour-suppressive pathway systemically.

• Active or suspected malignancy.
• Pregnancy, breastfeeding or active fertility treatment.
• Known hypersensitivity to recombinant proteins.

• redundantfollistatin-344 — Effectively the same active molecule once the signal peptide is cleaved.
• redundantace-031 — Both suppress the same signalling axis.

• · No validated marker. DEXA before and after is the only honest way to know whether anything changed.

Not approved for human use. Research-chemical status; prohibited in sport by WADA.

• Reviews of follistatin isoform biology and heparan-sulfate binding (FST-288 vs FST-315 vs FST-303) (review)
• Preclinical follistatin gene-delivery muscle hypertrophy studies (preclinical)

Everything in the follistatin-344 record applies here, because this is the same protein. The one distinction worth drawing out is the isoform biology, which is genuinely important and almost universally garbled in the market. Human follistatin exists as FS315 and FS288. FS315 carries an acidic C-terminal extension that folds back and masks a basic heparin-binding surface on follistatin domain 1. FS288 lacks that extension, so the heparin-binding surface is exposed and the protein sticks to heparan sulfate proteoglycans on cell membranes and in the basement membrane. The functional consequence is that FS288 is the paracrine, tissue-retained isoform that acts on the muscle it was made in, while FS315 is the endocrine, circulating isoform. Castonguay's work with a follistatin-288-Fc fusion showed exactly this - the heparin-binding version produces localised muscle growth. So if the goal is systemic myostatin and activin neutralisation, FS315 is the correct isoform. If the goal is a local effect at an injected muscle, FS315 is the wrong one, and yet it is the one sold for site injection. Ligand specificity is identical to FS344: myostatin, activin A, GDF11 and several BMPs, all trapped by wrapping the dimer and occluding the type II receptor face. Downstream, ActRIIB never signals, ALK4/ALK5 never phosphorylate Smad2/3, and the MAFbx/MuRF1 atrophy programme is not transcribed, while relief of Smad3 permits greater Akt activity.

The specific failure of FST-315 in practice is a category error: it is bought for local site injection when it is the isoform that does not stay local. The heparin-binding form that would act at the injection site is FS288, which is not what anyone is selling. Beyond that, the same three problems as FST-344 - no pharmacokinetics to anchor any dose, unmonitored FSH suppression, and a large, heavily disulfide-bonded, normally glycosylated protein that grey-market production has no realistic chance of folding correctly at scale. A misfolded follistatin is not just inert, it is more immunogenic than the correctly folded protein.

• Myostatin (GDF-8) — High-affinity direct ligand binding

  Sequestration; the ligand never reaches ActRIIA or ActRIIB.

• Activin A — High affinity - the original basis for follistatin's discovery and naming

  Sequestration, adding muscle effect beyond myostatin blockade and simultaneously suppressing pituitary FSH.

• GDF11 — Direct binding confirmed

  Sequestration of a close myostatin homologue with its own developmental roles.

• Heparan sulfate proteoglycans — Low for FS315 - the acidic C-terminal tail masks the heparin-binding site, which is the defining difference from FS288

  This is why FS315 circulates instead of being retained at the tissue where it was released.

No established timeline for any muscle effect from injected recombinant protein. If the product is active, FSH suppression would be detectable within two to four weeks, which makes it the only reliable early readout you have.

Identical considerations to follistatin-344, because it is the same protein. The only stacking note specific to this record is that running FST-344 and FST-315 together, which vendors encourage, is running one compound twice at double the price. If you are also using ACE-031, bimagrumab or an anti-myostatin antibody, you are stacking overlapping mechanisms with additive endocrine and vascular risk and no evidence of additive benefit.

Against follistatin-344, this is the same molecule after signal peptide cleavage, and paying for both is paying twice for one thing. Against FS288, which is the isoform that would actually make sense for local injection, FS315 is the circulating form - so the market has it backwards. Against ActRII-targeting biologics, follistatin's advantage is that it traps ligands rather than blocking receptors, which in principle spares any ActRII signalling driven by ligands follistatin does not bind; its disadvantage is that it also traps activin A and BMPs, which the selective antibodies do not, and it has essentially no human evidence while bimagrumab and apitegromab have hundreds of randomised subjects each.

$200–$700/month. Priced comparably to FST-344 despite being, in practical terms, the same secreted protein. 1 mg vials commonly 80-200 USD, and 100-200 mcg daily consumes 3-6 mg a month.

• ?No pharmacokinetic, bioavailability or dose-response data exist for injected recombinant follistatin-315 in humans.
• ?There is no human trial of follistatin-315 protein for any indication. The only human follistatin data are from AAV gene transfer of the FS344 construct.
• ?Whether grey-market material is correctly folded and disulfide-bonded is unknown, and this protein is unusually demanding in that respect.
• ?The degree and reversibility of FSH suppression at commonly used doses is unmeasured.
• ?Whether commercial 'FST-315' and 'FST-344' vials actually contain different molecules, or the same secreted protein under two names, has never been independently assayed.
• ?No molecular weight is given because it depends on expression system and glycosylation.

• Follistatin-288-Fc Fusion Protein Promotes Localized Growth of Skeletal Muscle Castonguay R, Camper M, Sako D, Kumar R, Elliott J, Schneyer AL, Liharska K, Davies MV, Cannell M, Grinberg AV, Liu H, Barron R, Buonopane M, Pearsall RS, Kumar R, Lachey J, Journal of Pharmacology and Experimental Therapeutics, 2019 · PMID 30563942

  The clearest demonstration of why the isoform matters: FS288, the heparin-binding form, drives localised muscle growth. FS315 is the one that circulates instead.

• Characterization of follistatin-type domains and their contribution to myostatin and activin A antagonism Cash JN, Angerman EB, Kattamuri C, Nolan K, Zhao H, Sidis Y, Keutmann HT, Thompson TB, Molecular Endocrinology, 2012 · PMID 22593183

  Which follistatin domains do what, and why selectivity between myostatin and activin A is not achievable with this scaffold.

• UniProtKB P19883 (FST_HUMAN) - Follistatin UniProt Consortium, UniProt Knowledgebase

  Confirms that isoform 1, synonym FS315, is the canonical 344-residue precursor with residues 30-344 forming the mature chain, and that FS288 is the alternative splice product.