In 1957, Margoshes and Vallee reported on the isolation of a protein

from horse kidney, which showed a high affinity for cadmium, and soon thereafter the

protein was named metallothionein (MT) by the leading scientists Ka¨ gi and Vallee.

Fifty years of intense research has dissected out many of the biochemical, molecular,

and genetic aspects of these proteins, yet not that much is understood on its physiological

putative functions. Being a highly conserved family of proteins would suggest essential

biological functions, but these may be dispensable and/or assumed by other

proteins as demonstrated by the phenotype of knock-out mice in normal conditions.

Nevertheless, under challenging conditions (such as tissue injury) a strong phenotype

appears that is suggestive of important physiological functions. This has been particularly

well shown in the brain, where antiinflammatory, antioxidant and antiapoptotic

effects of MT have been demonstrated. To date, the results gathered strongly support a

therapeutic value of these proteins that deserve attention in clinical studies.