THRA (thyroid hormone receptor alpha) is a ligand-dependent transcription factor that mediates cellular effects of thyroid hormones through heterodimerization with retinoid X receptor and binding to thyroid hormone response elements 1. While THRA can bind thyroid hormone, it functions as a weak dominant negative inhibitor of thyroid hormone action [UniProt]. THRA and THRB have distinct, non-overlapping physiological functions 2. THRA is expressed during early nervous system development 3 and regulates spatiotemporal responses in skin wound healing through phase-coupled mechanisms: epidermal THRA activates glutathione metabolism to accelerate reepithelialization, while dermal THRA mediates extracellular matrix maturation 4. Mutations in THRA cause resistance to thyroid hormone alpha (RTHΞ±), characterized by abnormalities in growth and gastrointestinal function with minimal effects on the hypothalamic-pituitary-thyroid axis, contrasting with RTHΞ² 2. THRA is predominantly expressed in tissues including heart and bone, where selective THRB activation is preferred therapeutically to avoid THRA-mediated side effects 5. Genome-wide analysis identified THRA as a potential therapeutic target for migraine treatment 6.