Palmer et al. (2001) found that Smpx-null mice had no obvious developmental defects in the heart or skeletal muscle, which indicated functional redundancy. However, after the identification of hearing loss-associated gene SMPX, there are no detailed reports on how this gene causes hearing loss in vivo. In this study, we established a progressive hearing loss mouse model via CRISPR-Cas9 (Jinek et al., 2012; Cong et al., 2013), which is highly consistent with the DFNX4 displayed in humans. The gene discussed is SMPX; the disease is hearing loss disorder.