Given the complexity of Wnt signaling in CLD, precision-targeted therapeutic strategies should consider: (i) cell-specific modulation, involving the development of selective Wnt regulators; (ii) combination therapies, such as integrating Wnt modulation with FXR agonists to maintain BA homeostasis; and (iii) timing of intervention, where Wnt activation may be beneficial in acute phases to promote repair, whereas inhibition may be more effective in chronic stages to prevent fibrosis progression. Here, NR1H4 is linked to congenital secretory chloride diarrhea 1.