SUMMARY Children with hearing loss have an increased risk for developing other disabilities. One commonly associated disability is Autism Spectrum Disorder (ASD), a condition that also includes alterations in the auditory system. Hearing loss might contribute to ASD core symptoms and interfere with communication, social interaction, and overall quality of life. Nearly 1 in 59 children with hearing loss were reported to receive school-based services for ASD. Mutations or deletions in the Myocyte-specific Enhancer Factor 2C (MEF2C) gene have recently been linked to ASD and other neurodevelopmental disorders. A preliminary study conducted in the candidate’s laboratory found that (1) Mef2c is highly expressed in auditory nerve macrophages in postnatal wild type mice, and (2) auditory nerve functional decline and hearing loss occur in a novel mouse model of a syndromic autism disorder, human MEF2C haploinsufficiency syndrome. The overall goal of this NIDCD Research Career Enhancement Award (K18) resubmission is to augment the candidate’s research expertise to study how peripheral auditory system deficits contribute to communication and other social behavior impairments in ASD and other common human developmental disorders. The candidate is an established auditory neuroscientist with more than 20 years of experience in the pathophysiology of the peripheral auditory system and resultant sensorineural hearing loss. With the mentorship of four leading experts from the Medical University of South Carolina and Harvard Medical School, the training plan and research project will provide the opportunity for the candidate to (1) acquire advanced scientific knowledge/research tools in the fields of neuroimmunology, neurodevelopmental disorders, central auditory processing and perception, and communication and social interaction behaviors; and (2) conduct a study to address the novel hypothesis that abnormal macrophage activity resulting from Mef2c deficiency leads to AN functional declines and hearing loss, and that these changes may be associated with abnormalities in higher levels of the nervous system and contribute to communication impairment and other autistic symptoms. These training and research activities will catalyze research collaborations in new directions and establish innovative research programs to study hearing loss and communication impairment in human neurodevelopmental disorders. These investigations will promote a greater understanding of the important role of cochlear macrophage and auditory nerve dysfunction in ASD and other neurodevelopmental disorders, and may reveal a neuro-immune based therapeutic strategy beneficial for this fast growing population.