Abstract Retinal ganglion cells (RGCs), like most neurons, heavily rely on functions fulfilled by mitochondria. However, for unclear reasons the sensitivity of RGCs to mitochondrial dysfunction is higher than in others neuronal types. As a result, many blinding diseases that affect RGCs are accompanied by mitochondrial impairment. These diseases have very different etiologies but likely share a common pathophysiology that involves some aspect of mitochondrial biology. Nevertheless, we have little knowledge of the processes that regulate RGC mitochondria in vivo which has impeded the development of mitochondria-directed treatments to promote RGC repair. It is important therefore to understand how RGCs regulate mitochondrial function and dynamics in vivo as a step in defining regulatory nodes amenable to pharmaceutical intervention. RGC axons appear to be a prime target for these interventions as they are especially sensitive to degenerative stress. In these axons that extend to a considerable distance, it is crucial that mitochondria are appropriately distributed to serve the needs of the periphery. We recently highlighted the importance of this distribution for RGC repair. We demonstrated that increasing mitochondrial transport protects RGCs from degeneration and promote axonal regeneration (Cartoni et al. 2016). This study uncovered a key regulator of mitochondrial transport; a mammalian specific mitochondrial protein called Armadillo Repeat-Containing X Linked Protein 1 (Armcx1). We showed that it regulates axonal mitochondrial transport and that it is both necessary and sufficient for RGC survival and axonal regeneration after optic nerve injury. These findings suggest that Armcx1 controls the mitochondrial distribution of a mitochondria based RGC repair program. Our long-term research goal is to elucidate and manipulate the elements of this newly identified repair program to treat vision disorders. Despite the importance of Armcx1 in RGC repair after traumatic injury, little is known about the physiological functions of Armcx1 in healthy and diseased RGCs. Our overall objective is to evaluate how Armcx1 impacts RGC degeneration and repair as well as to decipher how this protein regulates mitochondrial dynamics and function. Based on our preliminary results, our central hypothesis is that Armcx1 regulates mitochondrial transport in demanding conditions such as diseases and/or axonal outgrowth. Specifically, we hypothesize that Armcx1 is a ubiquitous player in neuroprotection (Aim 1) and that it is a critical component of the normal RGC axonal outgrowth program (Aim 2). Finally, in an effort to understand the mechanism by which mitochondria promote RGC repair, we will analyze the axonal and somatic mitoproteome and identify direct and indirect Armcx1-binding partners in vivo (Aim 3).