Recently, a mutation in RAC1 has been discovered in melanoma and ranked as the third most frequent hot spot gain-of-function mutation occurring in melanoma after those in BRAF and NRAS. This RAC1-P29S substitution releases the conformational restraint conferred by the conserved proline, which induces an increased binding of the protein to downstream effectors and promotes melanocyte proliferation and migration [57, 229]. Here, NRAS is linked to melanoma.