Nuclear distribution element-like 1 (Ndel1 or Nudel) was firstly described as a regulator of the cytoskeleton in microtubule and intermediate filament dynamics and microtubule-based transport. Emerging evidence indicates that Ndel1 also serves as a docking platform for signaling proteins and modulates enzymatic activities (kinase, ATPase, oligopeptidase, GTPase). Through these structural and signaling functions, Ndel1 plays a role in diverse cellular processes (e.g., mitosis, neurogenesis, neurite outgrowth, and neuronal migration). Furthermore, Ndel1 is linked to the etiology of various mental illnesses and neurodegenerative disorders. In the present review, we summarize the physiological and pathological functions associated with Ndel1. We further advance the concept that Ndel1 interfaces GTPases-mediated processes (endocytosis, vesicles morphogenesis/signaling) and cytoskeletal dynamics to impact cell signaling and behaviors. This putative mechanism may affect cellular functionalities and may contribute to shed light into the causes of devastating human diseases.
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