Thyroglobulin (TG) is a 330 kDa protein serving as the essential substrate for thyroid hormone synthesis. TG undergoes iodination of specific tyrosine residues followed by oxidative coupling in the thyroid follicle lumen to produce triiodothyronine (T3) and thyroxine (T4), with each TG dimer yielding seven thyroid hormone molecules 1. After TSH-stimulated internalization and lysosomal proteolysis, T3 and T4 are released and secreted into circulation 1. TSH regulates TG gene transcription through TSHR signaling, with internalization-dependent pathways controlling TG expression in human thyrocytes 2. TG is regulated by thyroid transcription factors TTF-1 and Pax-8 3. Mutations in the TG gene cause thyroid dyshormonogenesis and congenital hypothyroidism, with over 229 identified variants documented 4. Defective TG synthesis can result in intellectual disability and growth impairment if untreated 4. Dyshormonogenic goiters due to TG mutations may progress to thyroid carcinoma 3. Post-thyroidectomy TG measurement serves important diagnostic and prognostic roles in papillary and follicular thyroid carcinomas, predicting recurrence and metastatic potential 3. TG's pleiotrophic functions include tissue identification, differentiation assessment, and post-operative follow-up monitoring 3.