It functions in concert with two other thyroid hormone-binding proteins in the serum: In cerebrospinal fluid TTR is the primary carrier of T4.

Less than 1% of TTR's T4 binding sites are occupied in blood, which is taken advantage of below to prevent TTRs dissociation, misfolding and aggregation which leads to the degeneration of post-mitotic tissue.

Further association of two of these dimers in a face-to-face fashion produces the homotetrameric structure and creates the two thyroxine binding sites per tetramer.

[19][20][21] However, the monomer also must partially denature in order for TTR to be mis-assembly competent, leading to a variety of aggregate structures, including amyloid fibrils.

Treatment of familial (hereditary) TTR amyloid disease has historically relied on liver transplantation as a crude form of gene therapy.

[28] There is now strong genetic[29][30] and pharmacologic data (see European Medicines Agency website for the tafamidis clinical trial results) indicating that the process of amyloid fibril formation leads to the degeneration of post-mitotic tissue causing FAP and likely FAC and SSA.

[33] The reduced level of transthyretin in the CSF may indicate a lower thyroxine transport in brains of patients with schizophrenia.

[citation needed] As of March 2015, there are two ongoing clinical trials undergoing recruitment in the United States and worldwide to evaluate potential treatments for TTR amyloidosis.