Aminoacylase 1 (ACY1) deficiency is a rare autosomal recessive inborn error of metabolism traditionally associated with neurological manifestations and characteristic urinary N-acetyl amino acid excretion. The association between ACY1 variants and congenital hearing loss has remained incompletely characterized, with sensorineural hearing impairment documented in a minority of reported cases. This systematic review synthesizes evidence from 2000 to 2026 on splice variants in ACY1 and their relationship to congenital hearing loss, with particular focus on the recently characterized c.1063-1G>A splice-site variant and its downstream pathogenic mechanisms. We examine clinical, biochemical, and functional evidence from patient studies, in vitro splicing assays, and zebrafish models that collectively support ACY1 as a candidate gene for hereditary hearing impairment. Transcriptomic profiling reveals that ACY1 deficiency disrupts critical inner ear developmental genes, including gfi1ab and atoh1a/b, through mechanisms potentially involving aberrant BMP signalling pathway regulation. This review consolidates current knowledge, identifies knowledge gaps, and proposes a framework for understanding the molecular pathology of ACY1-related hearing loss. Clinical Presentation: The proband presented with bilateral sensorineural hearing loss of congenital onset. Notably, developmental milestones were normal over a 4-year follow-up period, distinguishing this case from many previously reported ACY1D patients who exhibited neurological symptoms including intellectual disability and motor delay. This observation suggests that hearing loss may occur as an isolated manifestation of ACY1 dysfunction, without the broader neurological phenotype typically associated with the condition.