Granulins are a family of growth factor proteins, which generally contain six disulfide bonds and are found in most organisms.1 They have diverse sequences and complex structure/function relationships.1 Select examples have potential as wound healing agents making it important to improve our understanding of how granulins fold and the structural features critical for bioactivity.2,3 Here we show, using structure-based design, chemical peptide synthesis and folding analysis, that independent folding of the N-terminal half of granulins might be a general phenomenon in the granulin family. By contrast, the C-terminal region does not fold independently in an analogous manner to the N-terminal region. We also show that the primary sequence might be more important than the three-dimensional structure for granulin bioactivity, which has implications for the design of novel wound healing agents.