Abstract Liver fibrosis results from chronic injury to the liver. There are several causes of liver fibrosis, including substance abuse (hepatotoxic agents), chronic infections and congenital metabolic disorders, which may trigger a series of synergistic and pro-fibrogenic events between parenchymal and non-parenchymal cells. Damaged hepatocytes undergo apoptosis after liver injury. This results in release of pro-fibrogenic mediators and inflammatory cytokines that will contribute to recruitment of inflammatory cells and subsequent activation hepatic stellate cells and Kupffer cells. Activation of pro-fibrogenic cells induces changes in extracellular matrix (ECM) protein composition, synthesis and degradation, and further release of pro-fibrogenic mediators. Tissue remodeling and ECM rearrangement in the liver are key events during hepatic fibrogenesis, and if the liver injury persist excessive accumulation of ECM proteins result in disruption of the liver architecture by formation of fibrous scars. The altered liver architecture can lead to portal vein hypertension, decreased metabolite flow and impaired liver function. If left untreated, liver fibrosis may progress into advanced hepatic fibrosis, also known as cirrhosis with an elevated risk of developing hepatocellular carcinoma. Hepatic fibrosis is a dynamic bidirectional process with both progression and regression. Fibrosis resolution can be achieved both spontaneously and therapeutically, but the most effective treatment is suppression or removal of the inflammatory stimuli. Glycosylated lysosomal membrane protein (GLMP), formerly known as NCU-G1, is a highly glycosylated bona fide lysosomal membrane protein with an unknown biological function. GLMP is highly conserved among species and ubiquitously expressed. A novel mouse model lacking GLMP has successfully been generated using a gene trap strategy. This Glmpgt/gt mouse model has no detectable expression of GLMP and is indistinguishable from wild type (WT) mice with regards to growth, behaviour and fertility. Glmpgt/gt mice spontaneously develop chronic liver injury which progresses into a well established fibrosis by the age of 6 months. To further characterize phenotypic alterations to the Glmpgt/gt mouse model caused by GLMP ablation gene expression analyses from new-born mice livers were conducted. Body weight gain and feed efficiency studies were carried out in both genotypes. Furthermore, confocal microscopy images of lysosomes and mitochondria in primary Glmpgt/gt lung fibroblasts and hepatocytes were analysed. Finally, possible alterations to metabolic homeostasis and cellular uptake were investigated. Glmpgt/gt mice are not born with liver fibrosis, but up-regulation of marker genes for fibrosis in 1 week old Glmpgt/gt livers compared to WT suggests that chronic liver injury and fibrogenesis are initiated early in life. WT and Glmpgt/gt mice show no obvious differences in body weight gain and have comparable feed efficiencies, although glucose metabolism is disturbed in Glmpgt/gt mice. Both lysosomes and mitochondria have altered morphology in primary Glmpgt/gt cells compared to WT, possibly caused by the ablation of GLMP. Glmpgt/gt hepatocytes also have a lower capacity of fluid-phase endocytosis compared to WT cells. This indicates perturbed lysosomal and mitochondrial function in Glmpgt/gt mice. Liver fibrosis is the main phenotypic characteristic of the Glmpgt/gt mouse model and may represent a new model for an unknown lysosomal disorder. This thesis demonstrated that lysosomal and mitochondrial abnormalities, and metabolic dysregulations result from GLMP ablation, and may be a contributor to the pathophysiology detected in Glmpgt/gt mice.