Thyroid hormone is essential for the normal function of virtually all tissues. 
The iodothyronine deiodinases catalyze the removal of an iodine residue from the 
pro-hormone thyroxine (T(4)) molecule, thus producing either the active form 
triiodothyronine (T(3); activation) or inactive metabolites (reverse T(3); 
inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last 
years, several studies have attempted to understand the mechanisms of D1 
function, underlying its effects on normal thyroid hormone metabolism and 
pathological processes. Although peripheral D1-generated T(3) production 
contributes to a portion of plasma T(3) in euthyroid state, pathologically 
increased thyroidal D1 activity seems to be the main cause of the elevated T(3) 
concentrations observed in hyperthyroid patients. On the other hand, 
D1-deficient mouse models show that, in the absence of D1, inactive and lesser 
iodothyronines are excreted in feces with the loss of associated iodine, 
demonstrating the scavenging function for D1 that might be particularly 
important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have 
been associated with changes in serum thyroid hormone levels, whereas decreased 
D1 activity has been reported in the nonthyroid illness syndrome and in several 
human neoplasias. The current review aims at presenting an updated picture of 
the recent advances made in the biochemical and molecular properties of D1 as 
well as its role in human physiology.