Driver mutations that promote melanoma progression include: the TElomerase Reverse-Transcriptase (TERT) promoter (progression into intermediate lesions and melanoma in situ), CDKN2A (gain of invasive potential), Phosphatase-and-TEnsin homologue (PTEN), tumor-protein p53 (TP53) (metastatic melanoma progression), Phosphatidylinositol-3,4,5-Trisphosphate Dependent Rac Exchange Factor 2 (PREX2) and its small GTPase substrate, (RAC1) (associated with melanocyte proliferation), and neurofibromin 1 (NF1) (typical for chronically sun-exposed skin or in older individuals). The gene discussed is PREX2; the disease is metastatic melanoma.