Follistatin 315

Follistatin 315 is a glycoprotein isoform of follistatin — a naturally occurring binding protein that acts as a potent antagonist of myostatin (GDF-8, Growth Differentiation Factor-8) and other members of the TGF-beta superfamily including activin. Myostatin is a negative regulator of skeletal muscle mass: it signals through the ActRIIB/ALK receptor complex to activate Smad2/3 transcription factors that suppress myoblast (muscle precursor cell) proliferation and differentiation, thereby limiting muscle growth. Follistatin 315 neutralises myostatin by binding it with high affinity (KD ~10^-10 M), preventing myostatin from engaging its receptor and thereby removing the brake on muscle cell differentiation and growth. The 315 isoform is the predominantly circulating form of follistatin, lacking the heparin-binding C-terminal domain present in the 344 isoform, giving it distinct pharmacokinetic and tissue distribution properties. By sequestering myostatin, follistatin 315 releases myoblasts from growth suppression, allowing enhanced muscle cell proliferation, differentiation into myotubes, and hypertrophy. The mechanism extends beyond myostatin: follistatin also binds activin A and BMP-family ligands, modulating the broader TGF-beta superfamily signalling that regulates not only muscle mass but also follicle-stimulating hormone (FSH) secretion and tissue inflammation.