NF2 and neoplasm: These studies have established that merlin exerts its tumor suppressive function in several cellular compartments: (1) at the cell membrane, by regulating growth factor receptor activation [45, 46] and extracellular matrix (ECM) contact-induced intracellular signaling [47]; (2) in the cytoplasm, e.g., by inhibiting signal transduction of the small G proteins Ras and Rac [48], as well as by inhibiting several kinases [46]; (3) in the nucleus, by suppressing the activity of the ubiquitin ligase CRL4DCAF1 [49] (Fig. 5).