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Understanding the biology of the previously underappreciated sensitivity of cochlear synapses to noise insult, and its clinical consequences, is becoming a mission for a growing number of auditory researchers. In addition, several research groups have become interested in developing therapeutic approaches that can reverse synaptopathy and restore hearing function. One of the major challenges to realizing the potential of synaptopathy rodent models is that current clinical audiometric approaches cannot yet reveal the presence of this subtle cochlear pathology in humans. This has catalyzed efforts, both from basic and clinical perspectives, to investigate novel means for diagnosing synaptopathy and to determine the main functional consequences for auditory perception and hearing abilities. Such means, and a strong concordance between findings in pre-clinical animal models and clinical studies in humans, are important for developing and realizing therapeutics. This paper frames the key outstanding translational questions that need to be addressed to realize this ambitious goal.Key components for translational models that support investigations relevant to synaptopathy.Table of pre-clinical publications to-date emphasizing histological synaptopathy data.Evidence that noise-induced synaptic damage in rat and chinchilla follow the same principles as do mouse and guinea pig.