NF2, also known as Neurofibromatosis type 2 gene, encodes the tumor suppressor protein Merlin, a member of the ezrin, radixin, and moesin (ERM) family [2,3,5,6]. Merlin regulates cytoskeleton and cell signaling, and is involved in crucial pathways such as the Hippo tumor-suppressive and mTOR pro-oncogenic signaling cascades [1]. The NF2 gene is of great biological importance as its inactivation is linked to tumorigenesis [1,2,3,5,6,7,8].

NF2 inactivation occurs in 30%-40% of mesotheliomas, potentially a late event conferring a more aggressive phenotype [1]. NF2 mutations are specifically associated with the development of schwannomas, meningiomas, and ependymomas [2]. Meningioma cells with NF2 inactivation are susceptible to Erastin-induced ferroptosis, and maintaining NF2 inhibits ferroptosis-related lipid peroxidation and cell death [4]. NF2-related schwannomatosis is characterized by the growth of benign nervous system tumors due to NF2 gene mutations and Merlin dysfunction [5]. In NF2 patients, mutations in the NF2 gene lead to loss of function of Merlin, strongly associated with the development of vestibular schwannomas and meningiomas [7]. NF2 gene mutations are implicated in over 11 different cancers, with 8 of them showing evidence of Hippo signaling cascade involvement [8].

In conclusion, NF2, through its product Merlin, plays a vital role in regulating cell-signaling pathways. Model-based research, especially studies on NF2 inactivation, has revealed its significance in various tumor-related diseases such as mesothelioma, schwannomas, meningiomas, and ependymomas. Understanding NF2 is crucial for elucidating tumorigenesis mechanisms and developing potential therapeutic strategies.