This website is for informational purposes only and does not constitute medical advice. Read disclaimer
Follistatin 315
A naturally occurring glycoprotein that inhibits myostatin and activin signaling, studied for muscle growth promotion and investigated as a potential therapeutic for muscle-wasting disorders.
Overview
Follistatin 315 (FST-315) is the predominant circulating isoform of follistatin, a single-chain glycoprotein that serves as a natural antagonist of activin and myostatin — both members of the TGF-β superfamily that negatively regulate muscle growth. Follistatin was originally identified in 1987 for its ability to suppress follicle-stimulating hormone (FSH) release from pituitary cells, but its potent myostatin-binding activity has since become its most therapeutically relevant property.
FST-315 (the number refers to the amino acid count of the mature protein) is the major circulating form, while FST-288 is a shorter splice variant that binds more tightly to cell surfaces through heparin-binding domains. Both forms bind activin and myostatin with high affinity, preventing these ligands from signaling through their receptors. By neutralizing myostatin's inhibitory signal, follistatin effectively removes the "brake" on muscle growth, allowing increased muscle fiber hypertrophy and hyperplasia.
The muscle-enhancing effects of follistatin overexpression have been dramatically demonstrated in animal studies. Mice with transgenic follistatin overexpression develop roughly double the normal muscle mass, and follistatin gene therapy delivered via adeno-associated virus (AAV) vectors has shown impressive muscle mass increases in non-human primates. Importantly, AAV-follistatin gene therapy has advanced to human clinical trials for inclusion body myositis and Becker muscular dystrophy, representing one of the most advanced gene therapy approaches for muscle disease.
Beyond muscle, follistatin has roles in liver biology, reproduction, and tissue repair. It is an acute-phase protein that increases dramatically after intense exercise and liver injury. The dual activity against both activin and myostatin gives follistatin a broader biological profile than specific myostatin inhibitors alone, which may be both an advantage (wider muscle-building effects) and a challenge (potential off-target effects on other activin-dependent processes).