The proposed AOP connects as the primary molecular initiating event the inhibition of the canalicular transporter ATP-binding cassette subfamily B member 11 (ABCB11) with various key events (e.g., bile acid accumulation, regulation of nuclear receptors, induction of inflammation, and oxidative stress) and intermediate steps (e.g., induction of apoptosis/necrosis and gene expression changes) to the adverse outcome, cholestasis. The gene discussed is ABCB11; the disease is cholestasis.