Collectively, these results suggest that elevated Gs signaling in ColI(2.3)+/Rs1+ mice, and possibly also in FD patients, may cause hyper-activation of osteocyte-mediated PLR as well as bone remodeling by osteoclasts and osteoblasts, ultimately leading to hearing loss by bony overgrowths that affect the conductive mechanisms of the ear. This evidence concerns the gene RS1 and Fabry disease.