More than a century ago, the very first adverse human health effects of metalloproteins were reported after the usage of cadmium-containing silver polishing agents. It was first observed in the Horse population. The discovery of the low-molecular-weight protein Metallothionein (MT) in 1957 was an important milestone as this protein was shown to bind cadmium and to cause cellular cadmium toxicity. The mentioned authors contributed evidence in the 1970s concerning cadmium binding to MT and synthesis of the protein in tissues. We showed in our previous studies that binding of cadmium to MT in tissues can prevent some toxic effects; yet, further, identification of these macro and micro-molecules is required at the biochemistry and genetics levels. As with the recent studies, novel biochemical functions of MTs are introduced, for example, a new application of Mts, which are being used in protein purification by affinity chromatography. The trend is used to cure neuron disorders and even cancer. This review summarizes that this evidence in a genetic experiment is still needed for find out the function of MTs; it is an open area of research even in the 21st century.