During NAFLD progression, SOX9<sup>+</sup> hepatocytes progressively expand and acquire transcriptional programs associated with inflammatory signaling and wound-healing processes.<h4>Conclusion</h4>Our findings highlight SOX9<sup>+</sup> hepatocytes as a dynamic and context-dependent hepatocyte subpopulation associated with adaptive metabolic responses during regeneration and altered inflammatory and wound-healing-related programs under chronic injury. This evidence concerns the gene SOX9 and metabolic dysfunction-associated steatotic liver disease.