A key aspect of skeletal muscle pathology in SBMA is functional denervation associated with upregulation of genes, such as muscle associated receptor tyrosine kinase (Musk), myogenin (MyoG), and neural cell adhesion molecule (NCAM), which are induced upon dysfunctional communication between the motor neuron and innervated myofiber10,16,28. Here, CHL1 is linked to Kennedy disease.