Protein stability enhances evolvability by increasing the ability of proteins to tolerate beneficial mutations. This was demonstrated using simulations with model lattice proteins, where extra stability allowed proteins to accept a wider range of beneficial mutations while still folding correctly. Experimental validation was done using cytochrome P450 BM3 variants, where a stabilized parent showed greater ability to tolerate destabilizing mutations that conferred new functions. The study shows that protein stability is crucial for evolution, enabling the discovery of new protein functions through directed evolution. It also suggests that natural evolution might similarly exploit this link. The research highlights the relationship between protein stability and evolvability, showing that more stable proteins are more robust to mutations and can evolve more effectively. The findings have implications for understanding natural protein evolution and improving protein engineering strategies.Protein stability enhances evolvability by increasing the ability of proteins to tolerate beneficial mutations. This was demonstrated using simulations with model lattice proteins, where extra stability allowed proteins to accept a wider range of beneficial mutations while still folding correctly. Experimental validation was done using cytochrome P450 BM3 variants, where a stabilized parent showed greater ability to tolerate destabilizing mutations that conferred new functions. The study shows that protein stability is crucial for evolution, enabling the discovery of new protein functions through directed evolution. It also suggests that natural evolution might similarly exploit this link. The research highlights the relationship between protein stability and evolvability, showing that more stable proteins are more robust to mutations and can evolve more effectively. The findings have implications for understanding natural protein evolution and improving protein engineering strategies.