Matching chemical properties to molecular biological activities opens a new perspective on l-ergothioneine.

l-ergothioneine is a low-molecular weight natural product, the chemical structure of which comprises oxygen-, nitrogen- and sulfur-containing functional groups. This gives l-ergothioneine specific physicochemical properties and allows a better understanding of its chemical reactivity, which is primarily due to the 2-thio-imidazole group. Here, a review is provided of how different modes of chemical reactivity account for the reported molecular biological activities of l-ergothioneine. By matching the physicochemical properties to the biological properties of l-ergothioneine, a new perspective of the function and the mode of action of this enigmatic molecule emerges.