It has been known that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes.

Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration.

[10] Several Dst mutant mouse lines have been described which share the common feature of having sensory neuron degeneration.

[11][12][13] In humans, loss of dystonin function can cause hereditary sensory and autonomic neuropathy type VI[14] and axonal Charcot-Marie-Tooth disease.

[15] In both human diseases, pathology is likely attributable to the loss of the dystonin-a2 protein isoform, which plays a role in neuronal autophagy.