The goal of this dissertation is to further understand two key, broad processes which occur over the course of a neuron's lifetime: its development and possible degeneration in disease. We identify novel components in both of these processes and attempt to understand the functional significance as well as the mechanism each component uses to exert its effects. We begin with work done focusing on how the neuron's dendritic tree develops. The development of neurons has two phases: (1) a first phase relying on a genetic program and (2) a second phase that uses synaptic activity to guide the fine tuning of connections. We are primarily interested in understanding how neurons develop within the motor system using cues from synaptic activity. One type of activity-dependent development in the motor system is driven by AMPA receptors assembled with the GluA1 subunit using the scaffolding protein, SAP97. In Chapter 2, we describe our finding that the small protein, CRIPT, functions in the development of the neuron's dendritic tree within the motor system. We show that CRIPT is expressed during the time in development when activity-dependent remodeling is occurring the in spinal cord. Additionally, we show that CRIPT binds to the PDZ3 domain of SAP97 using its C-terminus. Finally, we show that CRIPT is necessary for proper dendritic growth of the motor system and normal motor system responses in vivo. There are a number of diseases that specifically target motor neurons. One adult-onset disease is Amyotrophic Lateral Sclerosis (ALS). Like many neurodegenerative diseases, it is a multifactorial disease and a contributing factor is the lack of proper protein quality control and the formation of large protein aggregates within motor neurons. In Chapter 3, we focus on how endoplasmic reticulum-associated degradation (ERAD) components might affect mutant proteins in ALS and their toxicity. ERAD is responsible for maintaining the proper folding of proteins that are to be trafficked to the cell surface or secreted from the cell. Although many proteins associated with ALS are not ERAD substrates, a number of ERAD components have been found to interact with ALS-causing mutant proteins and have been found to be mutated in forms of familial ALS. We identify new modifiers within the ERAD pathway of the toxicity of two ALS-linked proteins, mutant TDP-43 and mutant SOD1. We focus on the mechanism of one suppressor of ALS-linked proteotoxicity, the loss of RAD-23. The levels of RAD23 are increased in ALS models and reducing RAD-23 levels can suppress phenotypes in ALS models, as well as suppress motor neuron toxicity of the mutant proteins. We further show that reduced RAD-23 is able to accelerate the turnover of mutant proteins associated with ALS. Finally, we show that there is a mislocalization of RAD-23 protein and increased RAD-23 protein expression in post mortem spinal cord tissue of ALS patients, suggesting that RAD-23 may be a new novel target in the treatment of ALS. Collectively, this work identifies and describes novel proteins and mechanisms involved in the development and pathobiology of motor neurons.