FRMD6 (FERM domain containing 6), also known as Willin, is a tumor suppressor and upstream regulator of the Hippo signaling pathway localized at the plasma membrane and cell-cell junctions 1. Mechanistically, FRMD6 activates MST kinase, leading to YAP/TAZ phosphorylation and inactivation 1, though it can also function through RTK inhibition independent of canonical Hippo signaling 2. FRMD6 regulates cellular fate decisions toward senescence via the Hippo-YAP-CCN3 axis, with expression controlled by p53 and SMAD transcription factors 1. In cancer contexts, FRMD6 downregulation is associated with poor prognosis across multiple malignancies including glioblastoma, thyroid cancer, and prostate cancer 234. FRMD6 restoration suppresses proliferation, invasion, and epithelial-mesenchymal transition while promoting apoptosis and cell cycle arrest 34. Beyond cancer, FRMD6 exhibits multiple neuronal functions including differentiation, myelination, and nerve injury repair 5, with genome-wide association studies identifying FRMD6 as a significant Alzheimer's disease risk gene 65. Following peripheral nerve injury, FRMD6 expression is dynamically regulated in dorsal root ganglia and spinal cord neurons 7.