Here, we demonstrated, for the first time, an association of ROS-producing fungi, such as C. albicans and C. glabrata with enhanced nuclear TG2 activity in hepatic cells leading to apoptosis, illustrating the impact of ROS-generating pathogens in inducing or exacerbating nuclear TG2-related liver injuries, which may provide a molecular mechanism of hepatic injury observed in ASH/NASH patients. Here, TGM2 is linked to metabolic dysfunction-associated steatohepatitis.