It is one of three transport proteins (along with transthyretin and serum albumin) responsible for carrying the thyroid hormones thyroxine (T4) and triiodothyronine (T3) in the bloodstream.

Of these three proteins, TBG has the highest affinity for T4 and T3 but is present in the lowest concentration relative to transthyretin and albumin, which also bind T3 and T4 in circulation.

In terms of genomics, TBG is a serpin; however, it has no inhibitory function like many other members of this class of proteins.

On the converse, in the presence of corticosteroids, which lower TBG levels, the total thyroid hormone (bound and free) in the blood will be low.

Thus, when the labeled hormone is added, since so little TBG is available in the blood, after equilibrium is achieved, only a small portion of it will bind, leaving plenty available for uptake by the resin.