PLS1 encodes Plastin 1, an actin-bundling protein essential for inner ear function and hearing. PLS1 mediates the liquid packing of actin filaments necessary for stereocilia formation and proper growth in sensory hair cells. The protein functions through its actin-binding domains (ABD1 and ABD2) to organize cytoskeletal structures critical for mechanoelectrical transduction in the inner ear 1. PLS1 mutations cause autosomal dominant non-syndromic hearing loss (DFNA76) through both loss-of-function and dominant-negative mechanisms 1. A splice-site variant (c.981+1G>A) causing exon 8 skipping disrupts intramolecular domain interactions, impairing actin bundle binding and stereociliary mechanoelectrical transduction (MET) channel activity 2. Pathogenic mutations have been identified across diverse populations, including a p.(Leu363Phe) variant in Hungarian Roma 3. In animal models, PLS1 mutations produce morphological defects in inner hair cells, reduced cochlear diameter, and impaired swimming behavior in zebrafish 2. Genetically, PLS1 variants contribute to both early-onset and age-related hearing loss, with rare variants in PLS1 identified in presbycusis cohorts 4. The clinical significance of PLS1 mutations extends to progressive hearing impairment in young adults, with evidence suggesting preservation of adult stereocilia is critical for maintaining normal hearing function 3.