Follistatin 344

Follistatin 344 is the longer isoform of follistatin, containing the full-length protein including the heparin-binding C-terminal domain that is absent in the 315 isoform. Like follistatin 315, follistatin 344 functions as a potent antagonist of myostatin (GDF-8) and activin, binding these TGF-beta superfamily ligands with high affinity to prevent their engagement with the ActRIIB/ALK receptor complex. The heparin-binding domain of follistatin 344 confers distinct properties: it enables binding to heparan sulphate proteoglycans in the extracellular matrix and on cell surfaces, localising follistatin 344 to tissue compartments and cell-surface microdomains where myostatin signalling occurs. This tissue-localisation property gives follistatin 344 a different pharmacokinetic and biodistribution profile compared to the predominantly circulating follistatin 315 isoform. By sequestering myostatin and activin at the tissue level, follistatin 344 removes the Smad2/3-mediated suppression of myoblast proliferation and differentiation, promoting skeletal muscle growth. The heparin-binding domain also influences follistatin 344's interaction with cell-surface proteoglycans that themselves modulate growth factor signalling, potentially expanding the peptide's regulatory footprint beyond simple myostatin neutralisation.