This review summarizes recent advances in understanding Gal-9's immunomodulatory mechanisms in chronic spontaneous urticaria pathophysiology, systemic lupus erythematosus, atopic dermatitis, melanoma, systemic sclerosis, herpes simplex virus infection, bullous pemphigoid, psoriasis, vitiligo, maculopapular exanthema, and skin grafting to provide a reference for future research. This evidence concerns the gene LGALS9 and melanoma.