Merlin-YAP signaling: emerging mechanisms, functions, and therapeutic approaches.

The Hippo signaling pathway has a critical role in regulating tissue growth, development, and tumor suppression. Mutations in NF2, which encodes the tumor suppressor Merlin, disrupt Hippo signaling, causing aberrant activation of YAP/TAZ and contributing to diseases, such as cancer and developmental disorders. Recent studies have identified novel mechanisms by which biomolecular condensation and phosphoinositides regulate Merlin function in Hippo signaling. Furthermore, NF2 deficiency sensitizes cells to ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation. In this review, I highlight the emerging roles of Merlin-YAP signaling in physiology and disease, focusing on its regulation through biomolecular condensates, its contribution to development and ferroptosis, and its implications for therapeutic interventions.