Gene-targeted and pathway-directed therapy in vitiligo: A scoping review of recent advances

Vitiligo is a chronic autoimmune depigmenting disorder with limited efficacy of conventional therapies. Recent advances in immunology and genetics have delineated specific pathogenic pathways amenable to targeted intervention. To systematically map and synthesize evidence on gene-targeted and pathway-directed therapies for vitiligo, including mechanistic, translational, and clinical evidence. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidance, systematic searches of PubMed, Embase, Web of Science, and Google Scholar (through November 2025) identified studies targeting genes or pathways in vitiligo. Eligible studies included mechanistic research, animal models, and human trials focusing on Janus Kinase (JAK)/Signal Transducer and Activator of Transcription, chemokine axes, Interleukin-15 (IL-15)/CD122, Heat Shock Protein 70 (HSP70), microphthalmia-associated transcription factor (MITF), programmed death-ligand 1 (PD-L1), and noncoding RNA interventions. Twenty-seven studies were synthesized across seven therapeutic clusters. Topical ruxolitinib (JAK1/2 inhibitor) achieved regulatory approval with demonstrated repigmentation in phase 3 trials. Six additional pathways, such as Interferon-γ–CXCL10–CXCR3 blockade, IL-15/CD122 antagonism, HSP70-based DNA immunotherapy, MITF mRNA, PD-L1 checkpoint enhancement, and microRNA-directed strategies, remain predominantly preclinical or early clinical stage. Gene-targeted therapy has transformed vitiligo into a model for precision dermatologic immunotherapy. Most approaches beyond JAK inhibition remain experimental and require rigorous long-term safety evaluation and comparative efficacy trials before clinical translation. Future directions include combination strategies, biomarker-driven patient selection, and integrated immune-modulating and regenerative approaches.