The mutation in BRAF kinase at V600 has been frequently reported in nearly 50% of melanoma patients resulting in the hyper-activation of MAPK pathway. As such, various inhibitors which target mutant BRAF have been developed including vemurafenib and dabrafenib both of which have demonstrated significant clinical outcomes. Nevertheless, both primary and acquired resistance reduce the overall response of patients to the therapy. So, the search of efficient biomarkers to stratify melanoma patients has become an imperative subject of research to enhance the efficacy of RAF inhibitor treatments and to decrease the rate of side effects due to the therapy. The mechanism of ubiquitination in controlling various functions such as stabilization of a protein cannot be neglected. A number of ubiquitin regulatory enzymes have been already shown to act on and regulate various component of MAPK pathway.