SBMA is caused by the expansion of a CAG/glutamine (polyQ) tract in the androgen receptor (AR) gene [1]. The glutamine tract is polymorphic in length, ranging from 9 to 36 amino acids in unaffected individuals. Expansions to 38 or more repeats cause disease, and the longer the CAG repeat, the more severe the phenotype [2, 3∗, 4]. SBMA belongs to the family of polyQ diseases, including Huntington's disease (HD), dentatorubral-pallidoluysian atrophy, and six types of spinocerebellar ataxia (SCA). Despite their clinical differences, polyQ diseases exhibit several common features. These diseases typically manifest in mid-life, even though the disease proteins are expressed from development throughout adulthood. Furthermore, these disorders are characterized by the accumulation of misfolded proteins in the forms of micro-aggregates (amyloid fibrils) and inclusions bodies, which represent a pathological hallmark of neurodegeneration. Protein misfolding and aggregation are not limited to neurons but also occur in peripheral tissues, including skeletal muscle (Figure 1). These abnormal protein species are often regarded as a characteristic feature of SBMA and other neurodegenerative disorders. However, there is ongoing debate regarding whether these aggregated proteins exert toxic effects or have a protective role. Additionally, polyQ diseases are characterized by the loss of specific neuronal populations, despite the widespread expression of the disease proteins and the fact that sometimes these proteins serve essential cellular functions. This selective vulnerability accounts for the distinct clinical presentations observed in these diseases. The AR mutation results in the progressive degeneration of lower motor neurons and myofibers, leading to weakness, fasciculations, and atrophy of skeletal muscle [5]. Moreover, patients often present with peripheral symptoms, including endocrine and metabolic abnormalities, making SBMA a multisystem disease [6,7]. As a matter of facts, analysis of liver in 15 enrolled patients will reveal pathogenetic pathways occurring in this peripheral tissue (Table 1).