Knotted proteins are proteins whose backbones entangle themselves in a knot. One can imagine pulling a protein chain from both termini, as though pulling a string from both ends. When a knotted protein is “pulled” from both termini, it does not get disentangled. Knotted proteins are interesting because they are very rare, and their folding mechanisms and function are not well understood. Although there have been some experimental and theoretical studies that hinted to some answers, systematic answers to these questions have not been found.