GDF-8/Myostatin is a secreted protein that is expressed in developing and adult skeletal muscle. It controls myoblast proliferation and is a potent negative regulator of skeletal muscle mass. It is upregulated in mechanically-stressed cardiomyocytes and induces the skeletal muscle wasting which is common in heart failure. The GDF-8 propeptide is cleaved from GDF-8 but remains associated and functions as an inhibitor of mature GDF-8. GDF-8 activity can also be inhibited through its association with Follistatin, FLRG, Decorin, or GASP-1. Active GDF-8 signals through a receptor complex containing Activin RIIB and either Activin RIB/ALK-4 or TGF-beta RI/ALK-5.