The goal of our laboratory is to define the molecular pathways necessary to maintain homeostasis in both developing and aging mammalian neurons. To do this we utilize forward genetics to identify mutations that are associated with loss of neurons in the aging mouse brain. To further dissect pathways underlying homeostatic disruption and disease, we also use forward genetics to identify genetic variants that enhance or suppress neural phenotypes. Our approach allows the identification, without a priori assumptions, of molecules critical for neuron homeostasis and survival, and indeed we have discovered disruptions in several novel pathways that were not previously associated with loss of neuronal function or survival. We are particularly interested in the role of alterations in translation elongation, translational fidelity, proteostasis, and RNA metabolism in neuronal function.