The modulation of these NF1-SPRED1/2-dependent downstream signaling effectors were further corroborated in Schwann cell models derived from Neurofibromatosis type I patients that consisted of either plexiform neurofibroma cells or unaffected nerve cells abrogated of NF1 or neurofibromin RAS-GAP activity. Here, NF1 is linked to plexiform neurofibroma.