Metabolic associated liver disease (MASLD) involves excessive hepatic lipid accumulation and affects an estimated 40% of Australian adults, contributing to the development of obesity, type-2 diabetes, and increased cardiovascular risk. When left untreated, MASLD can progress to metabolic associated steatohepatitis (MASH), characterized by inflammation and fibrosis, resulting in the permanent remodelling of the hepatic microenvironment. Prior to this stage, however, the liver has a remarkable ability to repair itself and may even regenerate back to full size if part of the liver is removed. Despite this, there are limited effective treatments for MASLD and MASH which can be attributed to a lack of thorough understanding regarding the causative agents responsible for its initial onset, subsequent advancement and the liver’s normal repair pathways. To investigate this, we conducted single-cell transcriptomics on livers from mice fed an AMLN diet, an intervention known to induce MASH as observed in humans. This was performed across 3 time points (2, 8 & 24 weeks) in both male and female C57BL/6J mice (n = 4/treatment). Overall, we analysed 88,000 cells at a depth of >20K genes across all conditions and identified more than 30 distinct cell populations. In addition, chronic exposure to AMLN diet stimulated a regenerative response with a number of novel gene targets identified that are likely involved in this process. We validated one of these targets (Nrg1) by utilising CRISPR and Lipid Nanoparticle technology to knock this gene out both in vitro and in vivo (Sox2-Cas9 mice). Preliminary studies showed that when fed a diet that induces liver injury (3,5-Diethoxycarbonyl-1,4-dihydrocollidine), Nrg1 knockout mice had smaller livers suggesting a reduced capacity for regeneration. This work proposes a regenerative role for NRG1 which may be manipulated for the treatment of MASLD.