TTR (transthyretin) encodes a tetrameric protein that primarily functions as a thyroid hormone-binding protein, transporting thyroxine from the bloodstream to the brain, and also participates in retinoid transport 1. The protein's pathological significance stems from its propensity for misfolding and amyloid formation. TTR tetramer dissociation is the rate-limiting step for aggregation, where destabilized tetramers lead to amyloid fibril deposition 2. Over 28 pathogenic TTR mutations cause hereditary transthyretin amyloidosis (ATTRv), characterized by extracellular amyloid deposition that destroys somatic and autonomic peripheral nervous systems, leading to progressive neuropathy and death 31. Wild-type TTR can also form amyloids in elderly individuals, causing senile systemic amyloidosis and cardiomyopathy 4. The V122I mutation affects 3-4% of African Americans and causes familial amyloid cardiomyopathy 4. Therapeutic approaches include TTR kinetic stabilizers like tafamidis and AG10 that prevent tetramer dissociation 24, and antisense oligonucleotides like inotersen and eplontersen that reduce TTR mRNA levels and protein synthesis 56. Recent evidence suggests TTR may also play protective roles in neuroinflammation and cognitive function 7.