Using this animal model combined with cellular and biophysical approaches, we have provided mechanistic insights into deafness caused by the ADGRV1 Y6236fsX1 mutation, delineated the architecture of the ALC and interactions between its components, and revealed that the phosphorylation of WHRN and ubiquitination of USH2A by the E3 ligase WDSUB1 play critical roles in the dynamic regulation of ALC. The gene discussed is USH2A; the disease is deafness.