During the last decade, c-jun N-terminal kinase (Jnk) emerged as central player in the pathophysiology of acetaminophen (APAP)-induced liver injury, especially in mice.1,2 Jnk activation and translocation of phosphorylated-Jnk (p-Jnk) to mitochondria was considered an amplification mechanism responsible for enhancing the mitochondrial oxidant stress to levels sufficient to trigger the mitochondrial permeability transition pore opening, a prerequisite for necrotic cell death.1,2 However, in a recent paper in Gastroenterology, Cubero et al3 reported that mice with the hepatocyte-specific knockout of Jnk1 and Jnk2 genes (JnkΔhepa) developed higher liver injury than wild-type animals after APAP overdose suggesting that Jnk activation may actually be beneficial in acute cell death.