Dysfunction in the mitochondria contributes to the development of acute liver injury (ALI). There is emerging evidence indicating the mitochondria is key to maintain liver homeostasis and survival; thus, controlling its functioning is important for the treatment of liver diseases. Recent findings have identified transcription factor zinc-finger and homeoboxes 2 (ZHX2) to be a critical modulator of liver postnatal gene expression, cell proliferation and lipid homeostasis in the liver.