The Nf1 gene, mutations of which are causative of Neurofibromatosis type 1 (NF1), codes for neurofibromin, whose major known function is to downregulate RAS, thus regulating the RAS/MAPK pathway [2]. NF1 is an autosomal dominantly inherited tumour predisposition syndrome, and Nf1 is of great biological importance as its heritable constitutional mutations lead to dysregulation of the RAS/MAPK pathway [2].

Most NF1 patients have private loss-of-function mutations scattered along the Nf1 gene [1]. A significant proportion of Nf1 missense mutations (30%) are deleterious by affecting pre-mRNA splicing [1]. Multiplex ligation-dependent probe amplification allows identification of restricted rearrangements that other methods might miss [1]. In addition, acquired somatic mutations in Nf1 are found in a wide variety of malignant neoplasms not associated with NF1, and Nf1 mutations are important in the acquisition of drug resistance in some cancers [2].

In conclusion, the Nf1 gene is crucial for regulating the RAS/MAPK pathway through the function of its product neurofibromin. Mutations in Nf1, both constitutional and somatic, are associated with NF1 and various malignancies, respectively. Understanding Nf1 through genetic models helps in comprehending the pathophysiology of related diseases and could potentially lead to improved diagnostic and therapeutic strategies.