Overall, our results indicated that a loss of Lrp6 function, such as rs2302685 in human subjects, Lrp6 haploinsufficiency in mice, and Lrp6 knockdown by siRNA in cells, was associated with hypofunction of Wnt/β-catenin-Cyp2e1 signaling, which resulted in a lower degree of liver injury associated with NAFLD as well as a reduced response to silibinin treatment (Figure 5F). Here, LRP6 is linked to metabolic dysfunction-associated steatotic liver disease.