Our principal findings are as follows: (1) significant downregulation of CUL3 and NRF2 in vitiligo tissues compared to controls; (2) upregulation of miRNA-146a, NF-κB, IL-6, and TNF-α, with concurrent downregulation of FOXP3; (3) strong correlations between CUL3, NRF2, FOXP3, and disease activity; and (4) molecular docking supporting the potential of vitexin as an NRF2 pathway modulator. Here, CUL3 is linked to vitiligo.