Indeed, depleting FKBP51 levels was shown to also reduce tau levels, while inhibiting its PPIase activity actually lead to increased stability of phosphorylated tau. Thus it is certainly possible that FKBP51 is involved in Alzheimer��s disease progression, since one of its earliest clinical features is depression. More recently, the extracellular protease neuropsin was shown to mediate anxiety-like behavior via an FKBP51 dependent mechanism. Thus, an important role for FKBP51 in maintaining proper brain function is emerging. Its relationship with major depressive disorder in HIV, bipolar disorder and possibly anxiety and Alzheimer��s disease further underlie its significance. Current treatment for depression includes the use of medications that extend the amount of time neurotransmitters are present in the synaptic cleft including serotonin, norepinephrine, and dopamine. It is estimated that 60�C70% of patients reach remission with the use of anti-depressant drugs. These low rates of efficacy have prompted research into other potential therapeutic targets in the HPA axis, particularly GR. However, there are many different isoforms of GR, making selective targeting with compounds challenging. Therefore, the results presented here show that FKBP51 may be the most appropriate target for treating depression via the modulation of the HPA axis in terms of its risk/benefit equation and potential therapeutic window. Also, and most noteworthy, because FKBP51 may act on the genetic liability to abnormal mood and anxiety states, it may provide a much needed treatment tool for secondary prophylaxis of depression recurrence and relapse. Dystonia is defined as abnormal involuntary movements that are prolonged, twisting in nature and frequently stereotypic and repetitive. Dystonia occurs as an isolated symptom without evidence of brain injury or as a consequence of pathologic insults to the basal ganglia or related structures. Primary and secondary dystonia may be treated with similar medications and both respond to deep brain stimulation therapy. These facts, and the characteristic dystonic postures that result from diverse etiologies, suggest that primary and secondary forms of dystonia may share a common downstream abnormality, perhaps a stereotyped disruption of basal ganglia output. The most common genetic form of primary dystonia, DYT1 dystonia, is a neurodevelopmental disorder caused by an in-frame deletion in the TOR1A gene that results in the loss of a glutamic acid in the C-terminus of torsinA. DYT1 dystonia is dominantly inherited but abnormal movements affect only 30% of mutation carriers. Despite this incomplete penetrance, 2-deoxyglucose studies show that all carriers exhibit abnormal brain metabolism, with increased metabolic activity in the cerebellum, putamen/globus pallidus, and supplementary motor cortex. Similarly, magnetic resonance diffusion tensor imaging shows white matter abnormalities associated