THRB encodes thyroid hormone receptor beta, a ligand-dependent nuclear receptor that mediates cellular responses to thyroid hormones (triiodothyronine and thyroxine) 1. As a member of the nuclear receptor superfamily, THRB functions as a heterodimer with retinoid X receptor, binding thyroid hormone response elements to regulate transcription of target genes 1. THRB mediates both canonical nuclear transcriptional effects and non-canonical cytosolic signaling pathway activation 2. The receptor is the predominant thyroid hormone receptor isoform in the liver, where it regulates metabolic homeostasis including lipid metabolism, glucose regulation, and protein synthesis 3. THRB mutations cause resistance to thyroid hormone beta (RTHβ), characterized by elevated serum thyroid hormone levels with inappropriately normal or elevated TSH and goiter 4. RTHβ exhibits variable phenotypic manifestation across tissues and individuals due to differential expression of mutant TRβ protein and tissue-specific compensation by THRA 45. Clinical features include attention deficit disorder, cardiac tachycardia, and hepatic metabolic dysfunction 6. THRB-selective thyromimetics, exemplified by the FDA-approved drug resmetirom, target hepatic THRB to treat metabolic dysfunction-associated steatohepatitis while minimizing cardiac and bone toxicity associated with THRA activation 3.