Willin/FRMD6: A Multi-Functional Neuronal Protein Associated with Alzheimer’s Disease

The FERM domain-containing protein 6 (FRMD6), also known as Willin, is an upstream regulator of Hippo signaling that has recently been shown to modulate actin cytoskeleton dynamics and mechanical phenotype of neuronal cells through ERK signaling. Physiological functions of Willin/FRMD6 in the nervous system include neuronal differentiation, myelination, nerve injury repair, and vesicle exocytosis. The newly established neuronal role of Willin/FRMD6 is of particular interest given the mounting evidence suggesting a role for Willin/FRMD6 in Alzheimer’s disease (AD), including a series of genome wide association studies that position Willin/FRMD6 as a novel AD risk gene. Here we describe recent findings regarding the role of Willin/FRMD6 in the nervous system and its actions in cellular perturbations related to the pathogenesis of AD.