While the origin and transcriptional profile of macrophage populations emerging in the liver upon NAFLD have been investigated thoroughly [7,8,9,10] and resulted in the identification of a TREM2+ subset, which is either termed LAM- [9,12] or NASH-associated macrophages (NAMs) [13] and Scar-associated macrophages (SAMs) [14], respectively, little is known about the mechanisms promoting the protective role of these TREM2+ macrophages. This evidence concerns the gene TREM2 and metabolic dysfunction-associated steatotic liver disease.