Given the importance of the RAS/AKT pathways in cancer, our findings should provide the molecular model and the rationale for developing CAPN1 inhibitors that halt NF1 destruction and, therefore, block RAS activation, downregulate AKT signaling, which may be useful as a therapeutic strategy in melanoma, and possibly also in other cancers, where NF1 expression is destabilized. Here, AKT1 is linked to melanoma.