Transthyretin (TTR) is a tetrameric transport protein highly conserved through vertebrate evolution and synthesized in the liver, choroid plexus, and retinal pigment epithelium. TTR transports the thyroid hormone thyroxine and the retinol-binding protein (RBP) bound to retinol (vitamin A). Mutations in TTR are associated with inherited transthyretin amyloidosis (ATTRv), a progressive, debilitating disease that is ultimately fatal and is characterized by misfolding of TTR and aggregation as amyloid fibrils, predominantly leading to cardiomyopathy or polyneuropathy depending on the particular TTR mutation. Transthyretin amyloid cardiomyopathy can also occur as an age-related disease caused by misfolding of wild-type TTR. Apart from its transport role, little is known about possible additional physiological functions of TTR. Evidence from animal model systems in which TTR has been disrupted via gene knockout is adding to our cumulative understanding of TTR function. There is growing evidence that TTR may have a role in neuroprotection and promotion of neurite outgrowth in response to injury. Here, we review the literature describing potential roles of TTR in neurobiology and in the pathophysiology of diseases other than ATTR amyloidosis. A greater understanding of these processes may also contribute to further clarification of the pathology of ATTR and the effects of potential therapies for TTR-related conditions.