In mouse models, both mutation (S1PR2stdf/stdf) and knockout of S1PR2 (S1PR2–/–) result in progressive hearing loss, essentially starting at 2–4 weeks postnatally with varying degrees of hearing impairment to complete deafness, which is characterized by the defect of SV at the onset and followed by decreased intracochlear potential (EP) and subsequent loss of HCs and SGNs (Herr et al., 2007, 2016; Kono et al., 2007; Ingham et al., 2016). The gene discussed is S1PR2; the disease is deafness.