TG and hypothyroidism: It is now recognized that patient and animal models expressing genetically encoded misfolded mutant thyroglobulin (TG, the protein precursor for thyroid hormone synthesis) exhibit dramatic swelling of the endoplasmic reticulum (ER), with ER stress and cell death in thyrocytes — seen both in homozygotes (with severe hypothyroidism) and heterozygotes (with subclinical hypothyroidism).