These two different floxing strategies resulted in opposite results on HMGB1 and mitochondrial quality control and autophagy mechanism in vivo,30, 42 but similar outcomes in liver cancer progression19, 43 without really finding a rational molecular explanation.44, 45, 46 Further studies will be needed to decipher why both transgenic lines lead to similar conclusions in certain contexts and to opposite conclusions in specific settings. The gene discussed is HMGB1; the disease is liver cancer.