Hepatic cell-specific expression patterns, molecular mechanisms, and therapeutic targeting strategies of solute carrier transporters in drug-induced liver injury

Drug-induced liver injury (DILI) is a common and mechanistically complex adverse drug reaction in clinical practice and is one of the major causes of drug development failure and post-marketing drug withdrawal. Solute carrier (SLC) transporters constitute a large membrane protein superfamily comprising more than 400 members that are widely distributed across the plasma membrane and organelle membranes. They represent the second-largest membrane protein family in the human genome, surpassed only by G protein-coupled receptors (GPCRs). SLC transporters exhibit distinct cell-specific expression patterns across different hepatic cell types. Their substrates include not only drugs but also various endogenous metabolites, such as bile acids, amino acids, and lactate. Therefore, SLC transporters play important regulatory roles in the pathogenesis of DILI. This review systematically summarizes the expression patterns of major SLC transporters in different hepatic cell types and discusses their roles and underlying mechanisms in DILI initiation, inflammatory amplification, cholestasis, and fibrotic progression. Recent advances in SLC-related pharmacological agents and therapeutic targeting strategies are also reviewed. SLC transporters not only influence intrahepatic drug exposure but also participate in metabolic–inflammatory coupling within the multicellular hepatic network, suggesting that they may serve as important targets for DILI risk prediction and precision intervention.