THADA (THADA armadillo repeat containing) functions as a regulatory component of the FTSJ1 complex, mediating 2'-O-ribose methylation at position 32 of the tRNA anticodon loop, a modification crucial for accurate translation 1. Beyond its tRNA methylation role, THADA regulates calcium homeostasis by reducing endoplasmic reticulum (ER) Ca2+ stores through inhibition of SERCA2-mediated calcium re-uptake and induction of RyR2-dependent calcium leakage 2. This calcium dysregulation has significant metabolic consequences: THADA is strongly activated in type 2 diabetes mellitus (T2DM) islets, where it impairs β-cell function and promotes ER stress-induced apoptosis via interaction with the pro-apoptotic DR5-FADD-caspase-8 complex 2. THADA knockout mice demonstrate improved glycemic control, enhanced insulin secretion, and preserved β-cell mass, with THADA inhibition protecting against diet- and streptozotocin-induced hyperglycemia 2. Beyond diabetes, THADA genetic variants associate with prostate cancer susceptibility and progression across multiple populations 3, and show evolutionary evidence of positive selection in polycystic ovary syndrome 4. THADA also influences FSH pharmacokinetics during fertility treatment, with specific genotypes affecting drug distribution 5. These findings establish THADA as a promising therapeutic target for metabolic disorders, particularly type 2 diabetes.