For the treatment of NASH, a THR-β agonist ideally needs to achieve three goals: 1) reduced hepatic steatosis, inflammation and fibrosis; 2) liver specificity with no effect on the hypothalamus-pituitary-thyroid axis, which regulates serum thyroid levels; 3) high THR-β selectivity to limit off-target THR-α effects on the bone/cartilage and heart. The gene discussed is THRB; the disease is metabolic dysfunction-associated steatohepatitis.