Neurons are a most suitable cellular system to dissect the mechanisms implicated in survival-function homeostasis in the post-mitotic stage. In fact, neurons become permanently arrested in the G0 phase early in development and from this time, these postmitotic cells are exposed to the constant presence of stress byproducts derived from the intense metabolic needs of the brain. Still, the total number of neurons does not significantly decrease with age, implying that a major effort in the biology of these cells is dedicated to warrant cell survival. Consistent with their post-mitotic quiescence, telomere length in neurons does not change with age. However, TERT does SP600125 remains abundant in the fully differentiated neuron, suggesting that neuronal TERT may play a telomere-independent role. In agreement with this possibility, work in cancer cells and in experimental paradigms of brain excitotoxicity have suggested a mitochondria associated, pro-survival function. In this work, we have investigated the possibility that a similar mechanism may be part of the constitutive survival machinery of aging neurons. Our data show that TERT plays a pro-survival role in fully differentiated neurons through its association to RNA granules, where it contributes to the translational control of the pro-survival gene p15INK4B. Therefore, we performed gain and loss-offunction experiments in cultured hippocampal neurons. Figure S2 shows that TERT knock-down in fully differentiated neurons increased apoptosis. On the contrary, over-expression exerted an anti-apoptotic role. This last effect was prevented by pre-treating cells with the nuclear export inhibitor Leptomycin B, implying that the pro-survival effect requires TERT that previously accumulated in the nucleus. Antibody specificity was verified by western blot analysis: Figure S4 shows the Fulvestrant concentration-dependent increase of a band at the expected molecular weight. Moreover, knock-down with two different shRNA against TERT and over-expression experiments prove, respectively, the loss and the increase of the target protein. To elucidate the mechanisms behind the pro-survival role of TERT in differentiated neurons, we analyzed TERT cytoplasmic localization using mouse brain sub-cellular fractionation, prepared as in Gray and Whittaker. Western blot analysis from adult mouse and rat brains revealed high levels of the protein in the microsomal and ribosomal fractions. In support of the biochemical data, immunofluorescence microscopy in fully differentiated hippocampal neurons in vitro revealed the colocalization of TERT with the p58 protein, a canonical ERGIC marker.