Misfolded Transthyretin as a Novel Risk Factor for Heart Failure: A Rich History With Implications for Future Diagnosis and Treatment

Transthyretin, a circulating, 127–amino acid protein predominantly synthesized by the liver, has a rich history. Initially discovered in the late 1940s and early 1950s, transthyretin was previously called prealbumin, a widely known protein, given its clinical use as a marker of nutritional status.¹ The name prealbumin stemmed from the initial recognition that it migrated ahead of albumin on gel electrophoresis.² By 1960, the role of prealbumin as a transporter of thyroxine was discovered, and in the late 1960s and early 1970s, a more important role for prealbumin was identified. Prealbumin formed a complex with retinol-binding protein, which in turn is bound to vitamin A.¹ Based on these discoveries, the name transthyretin (transporter of thyroxin and retinol-binding protein) was officially adopted in 1980.¹