Non-alcoholic fatty liver disease (NAFLD) is a clinicalpathological term that includes a spectrum of alterations ranging from the simple accumulation of triglycerides in the hepatocytes (steatosis) to steatosis with hepatic inflammation (steatohepatitis or NASH). NASH, in turn, also progresses to cirrhosis and HCC. The mechanisms that lead to the expression of NASH are not clear, but it is a condition associated with obesity, insulin resistance, and diabetes. Since the incidence of these diseases is increasing, the prevalence of NASH is also expected to increase in coming years (today it varies between 13 to 15 % of the population). NASH is now considered to be an emerging disease in USA and occidental countries.Nowadays, lacking accurate, sensitive diagnostic test, distinguishing steatosis from steatohepatitis requires the use of invasive techniques like liver biopsy. To summarize, the lack of information about the factors implicated in the NASH pathogenesis, as well as in the prognostics characteristics and the treatment of this pathology, highlights the need of new approach in order to understand the mechanisms involved in the development of NASH and the progression to cirrhosis and liver cancer. Over the last few years, we have elucidated new molecular mechanisms implicated in the proliferation, regeneration and apoptosis and identified targets that contributing to the abnormal hepatic lipid metabolism and proliferation ended in the development of cirrhosis and liver cancer.The most important projects ongoing in my laboratory are focused on the role of posttranslational modifications throughout different stages of liver disease and ranges from effects on whole organ, such as NEDD8 inhibition on development of fibrosis, to more molecular approaches such as autophagy in hepatic steatosis and the role of LKB1 in hepatocellular carcinoma. In this respect, Metabolism has been one of the most important goals as well as the mitochondria function in liver disease. Finally we have maintained a closed collaboration with the company OWL Metabolomics in the development of OWLiver® Care and OWLiver®, two non-invasive assays for fatty liver screening and for NASH diagnosis and Millennium Pharmaceuticals and Mitotherapeutix for the discovery of new drugs for the treatment of cirrhosis-NAFLD dependent and Liver Cancer.