Thus, as expected, mice deficient in cysteine cathepsins, Ctsb-/- or Ctsl-/-, show accumulation of Tg in thyroid follicles due to its impaired proteolytic solubilization and degradation, while Ctsl-/- and Ctsk-/-/Ctsl-/- mice exhibit decreased serum concentrations of free T4 indicating hypothyroidism [20]. Here, CTSL is linked to hypothyroidism.