Neurofibromin signaling pathway regulation. The NF1 gene product, neurofibromin, functions as both a negative regulator of RAS activity (RAS GAP) and as a positive regulator of AC activity. Impaired neurofibromin function leads to increased RAS activation, resulting in high levels of RAF/MEK and AKT/mTOR signaling. Similarly, reduced neurofibromin function is associated with decreased cAMP levels and reduced protein kinase A (PKA) activity. GRD, GAP-related domain.