We comprehensively investigated the impact of sensory neuron Gb3 deposits in the α-GAL deficient mouse model as a potential basis of small fiber neuropathy in FD and detected three major effects: Gb3 is age-dependently associated with (1) increased BiP expression indicating endoplasmic stress and nerve fiber degeneration, (2) increased neuronal TRPV1 protein expression and sustained capsaicin responsiveness in vivo, and (3) reduced neuronal Ih and Nav1.7 currents associated with a lack of thermal and mechanical hypersensitivity after nerve lesion and inflammation. This evidence concerns the gene SCN9A and Fabry disease.