LBHBs are a special case of hydrogen bonds formed between polar atoms with comparable pKa values and characterized by delocalization of a proton that becomes equally shared. The existence of LBHBs in proteins is debated. Neutron crystallography is able to unambiguously reveal such interactions within protein structures. Despite progress, no such structures are currently available for cholinesterases. Most predictions on LBHBs come from Born-Oppenheimer QM/MM calculations. Such calculations are incapable of modeling proton tunneling and are believed to provide heightened proton transfer barriers. Taking into account these limitations, researchers suggest that computed barriers of <2 kcal/mol may hint on potential LBHBs. In this study, for the concerted transfer of two protons we obtained the PBE estimate of the barrier of 1.65 kcal/mol (Figure ). Therefore, there may be a possibility that cholinesterases harbor a conjugated pair of two LBHBs, a structural unit never reported for proteins before. Further studies, both experimental and computational -with larger QM regions, polarizable embeddings, and accounting for nuclear quantum effects -are needed to scrutinize this hypothesis. Some structurally similar enzymes feature even more titratable residues in their extended active sites (Figure ), which may add further complexity to the issue.