Through a combination of single-cell/single-nucleus RNA-Seq data analysis and IHC studies of liver tissue samples obtained from patients with MASH and two mouse models of MASH, Liu et al. detected pathogenic macrophages characterized by TET3 overexpression (hereafter referred to as Toe-Macs) in MASH livers, which express NLRP3, IL-1β, TGF-β1, CCL2, and IL-6. Here, TET3 is linked to metabolic dysfunction-associated steatohepatitis.