Growth differentiation factor 11 (GDF11), a member of the transforming growth factor β (TGF-β) family, plays diverse roles in mammalian development. It is synthesized as a large, inactive precursor protein containing a prodomain, pro-GDF11, and exists as a homodimer. Activation requires two proteolytic processing steps that release the prodomains and transform latent pro-GDF11 into active mature GDF11. In studying proteolytic activation in vitro, we discovered that a 6-kDa prodomain peptide containing residues 60-114, PDP, remained associated with the mature growth factor. Whereas the full-length prodomain of GDF11 is a functional antagonist, PDP had no impact on activity. The specific activity of the GDF11/PDP complex (EC = 1 nM) in a SMAD2/3 reporter assay was identical to that of mature GDF11 alone. PDP improved the solubility of mature GDF11 at neutral pH. As the growth factor normally aggregates/precipitates at neutral pH, PDP can be used as a solubility-enhancing formulation. Expression of two engineered constructs with PDP genetically fused to the mature domain of GDF11 through a 2x or 3x G4S linker produced soluble monomeric products that could be dimerized through redox reactions. The construct with a 3x G4S linker retained 10% activity (EC = 10 nM), whereas the construct connected with a 2x G4S linker could only be activated (EC = 2 nM) by protease treatment. Complex formation with PDP represents a new strategy for stabilizing GDF11 in an active state that may translate to other members of the TGF-β family that form latent pro/mature domain complexes.