Follistatin-315

Follistatin-315 is the primary circulating isoform of follistatin, a glycoprotein that binds and neutralizes members of the TGF-β superfamily, most notably myostatin (GDF-8) and activin A. FST-315 is produced by alternative splicing and accounts for approximately 95% of circulating follistatin. Unlike the tissue-bound FST-288 isoform, FST-315 has lower heparin affinity and acts systemically, making it the dominant endocrine regulator of muscle mass.

Follistatin-315 binds myostatin and activin A with nanomolar affinity (Kd ~5–10 nM), forming high-affinity complexes that prevent ligand binding to the ActRIIB/ALK4/5 receptor complex on muscle satellite cells. By blocking myostatin signaling, FST-315 disinhibits Smad2/3-mediated suppression of muscle protein synthesis, promoting myofiber hypertrophy and satellite cell proliferation. It also inhibits activin A signaling in bone, gonads, and brain, producing broader endocrine effects beyond skeletal muscle.

Follistatin overexpression in mice produces 200–300% increases in muscle mass without apparent toxicity in early studies. Intramuscular gene therapy with follistatin AAV vectors has been evaluated in Becker muscular dystrophy Phase 1/2 trials (Mendell et al.). Recombinant FST-315 peptide injection studies show shorter-acting effects (~90-minute half-life) vs. gene therapy, limiting practical utility. Research in sarcopenia and metabolic disease is active.

Peptides commonly paired with Follistatin-315 for synergistic effects.