GPNMB originally identified in melanoma in 1995 (Hoashi et al., 2010), has been recognized as a pleiotropic regulator modulating both physiological homeostasis and disease pathogenesis through its multidomain structure containing an RGD integrin-binding motif, PKD domain, and hemITAM signaling motif (Theos et al., 2013). This evidence concerns the gene GPNMB and melanoma.