The most active standard-of-care therapies for patients with advanced melanoma are divided into two categories, each with its own unique properties and characteristics: (i) small molecule targeted therapy inhibiting aberrant signaling in the mitogen-activated protein kinase (MAPK) pathway, and (ii) immune checkpoint inhibitors, with monoclonal antibodies targeting the programmed death receptor 1 (PD-1) and the cytotoxic T lymphocyte antigen-4 (CTLA-4)1–3. Here, WNK2 is linked to melanoma.