Follistatin-315

Muscle Growth / Hormonal

Also known as: FST-315, FS-315, Circulating Follistatin

FollistatinsResearch phase: Preclinical (gene therapy approaches in clinical trials)Regulatory: Endogenous protein. Not approved as a therapeutic. FS-344 gene therapy (via AAV vectors) has entered early clinical trials for muscle disorders.

Mechanism

Follistatin-315 is the main circulating form of follistatin in the body. It blocks myostatin and activin — two proteins that limit muscle growth — acting as a natural muscle-growth promoter. Unlike follistatin-344 (the research form), FS-315 has a heparin-binding domain that is partially masked, giving it a longer circulating half-life and more systemic distribution rather than tissue-localized effects.

Technical detail

Follistatin-315 (FS-315) is the predominant circulating isoform generated by alternative splicing of the FST gene. It contains a C-terminal acidic tail that partially masks the heparin-binding site on domain I, reducing cell-surface proteoglycan binding and increasing circulatory bioavailability compared to FS-288. FS-315 neutralizes activin-A and myostatin (GDF-8) by forming high-affinity irreversible complexes, preventing their binding to ActRIIB and subsequent Smad2/3 signaling that would otherwise inhibit myogenic differentiation. Also binds GDF-11 and other TGF-beta ligands with lower affinity.

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