 CA2 plus overload-induced mitochondrial dysfunction is considered a contributing factor alcohol-associated liver disease pathogenesis. Here the authors report that PDK4 promotes CA2 plus, channeling complex formation at the endoplasmic reticular mitochondria contact sites, which contributes to the pathogenesis of alcohol-associated liver disease in studies with male mouse and hepatocyte models. This article was authored by the Ms Thao Dam, Dipanjan Chanda, Jung Yuli, and others.