Recent research has shown that TLR4 mediates the MVB-lysosomal signaling pathway, which affects inflammation, IR, and impaired glucose metabolism, exacerbating NASH, which can be inhibited by ubiquitination of Tmbim1 by the E3 ubiquitin ligase Nedd4L (89) (Figure 2). The gene discussed is NEDD4L; the disease is metabolic dysfunction-associated steatohepatitis.