Abstract
Genetic liver diseases encompass a heterogeneous group of conditions that disrupt hepatic development, structure, or function. Advances in high-throughput sequencing have revealed the molecular basis of many disorders previously defined only by clinical or biochemical features, transforming diagnostic and therapeutic approaches. This review proposes a mechanistic framework that distinguishes diseases arising from developmental abnormalities from those caused by functional impairments in hepatocellular or biliary physiology. It outlines how defects in transporters, enzymes, signaling pathways, intracellular trafficking, and mitochondrial function converge to produce diverse hepatic phenotypes. Moreover, translational aspects are discussed such as how the growing integration of genetic testing into clinical practice enables precise diagnosis, informs prognosis and therapy, and refines disease classification. Finally, the review discusses future directions in the field, emphasizing the role of multi-omic approaches, organoid modeling, and data sharing in elucidating unresolved pathogenic mechanisms and advancing precision hepatology.