HOMER2 is a postsynaptic scaffolding protein essential for normal hearing and synaptic function. The protein contains an EVH1 domain and coiled-coil domain that are critical for multimerization and protein interactions 1. HOMER2 localizes to stereocilia of inner ear hair cells and regulates intracellular calcium homeostasis and cytoskeletal organization 1. The protein's coiled-coil domain is essential for multimerization and interaction with CDC42, processes crucial for normal auditory function 2. Pathogenic variants in HOMER2 cause autosomal dominant non-syndromic hearing loss (DFNA68), with frameshift mutations leading to progressive sensorineural hearing loss requiring cochlear implants in older adults 32. Mouse models confirm that Homer2 deletion causes early-onset rapidly progressive hearing loss 1. Beyond auditory function, HOMER2 interacts with amyloid precursor protein and inhibits Aβ peptide production, suggesting a potential protective role against Alzheimer's disease pathology 4. The protein also shows elevated expression in certain cancers, where it may serve as a prognostic marker 5. HOMER2 variants are increasingly recognized as causes of auditory neuropathy spectrum disorders through genetic screening approaches 6.