Oxysterol binding protein like 2 (OSBPL2),an important regulator in cellular lipid metabolism and transport,was identified as a novel deafness-causal gene in our previous work.To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotypephenotype associations,the OSBPL2-disrupted Bama miniature (BM) pig model was constructed using CRISPR/Cas9-mediated gene editing,somatic cell nuclear transfer (SCNT) and embryo transplantation approaches,and then subjected to phenotypic characterization of auditory function and serum lipid profiles.The OSBPL2-disrupted pigs displayed progressive hearing loss (HL) with degeneration/apoptosis of cochlea hair cells (HCs) and morphological abnormalities in HC stereocilia,as well as hypercholesterolaemia.High-fat diet (HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia,The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss (NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.