Natural selection results in protein sequences that are only soluble to the level that is required to carry out its physiological function. However, in biotechnological applications, we need these proteins to survive concentrations that are up to 1000-fold higher that what naturally occurs, e.g. an antibody drug in the syringe prior to injection. Because of this, biotechnological and therapeutic applications of protein are often hampered or rendered impossible by the mismatch between the natural solubility of a protein and the requirements of the application. This raises the question whether the solubility of natural protein sequences could be improved without affecting their intended function.