Plerixafor Biases CXCR4 Signaling Through β-Arrestin to Promote Melanogenesis via β-Catenin–MITF Activation

The study demonstrates that plerixafor, a β-arrestin–biased CXCR4 ligand, enhances melanogenesis by activating β-catenin–MITF transcriptional programs, increasing MITF and tyrosinase expression in melanocytes. In vitro experiments with PIG1 cells and in vivo tests on a hydroquinone-induced depigmentation mouse model showed improved repigmentation and hair follicle regeneration without inflammation or toxicity. These findings suggest plerixafor's potential as a therapeutic agent for pigmentation disorders by modulating CXCR4 signaling and activating melanogenic pathways. Further research is needed to explore its use in combination with standard therapies for repigmentation.