Considering that de novo HLA-G expression at high levels could support an immunosuppressive response in pathological conditions, such as cancer and viral infections, and the HLA-G downregulation expression could impair the HLA-G mediated control of the immune response leading to autoimmunity [88], the correlation between higher HLA-G and lower LILRB1 levels and vitiligo is here suggested as a hypothesis of a mechanism associated with impaired control of immune response at the skin level. The gene discussed is HLA-G; the disease is vitiligo.