DYSF is upregulated and exhibits a potential role along with that of HLA-A and MCP-1 in inflammatory cell infiltration and muscle damage during the development of DM/PM.
The deficiency in dystrophin and drastic reduction in dystrophin-associated proteins appears to trigger (i) enhanced membrane repair involving myoferlin, dysferlin and annexins, (ii) increased protein synthesis and the compensatory up-regulation of cytoskeletal proteins, (iii) the decrease in the scaffolding protein periaxin and myelin PO involved in myelination of motor neurons, (iv) complex changes in bioenergetic pathways, (v) elevated levels of molecular chaperones to prevent proteotoxic effects, (vi) increased collagen deposition causing reactive myofibrosis, (vii) disturbed ion homeostasis at the sarcolemma and associated membrane systems, and (viii) a robust inflammatory response by the innate immune system in response to chronic muscle damage.
However, animal models fail to fully reproduce the disease severity observed in humans, with dysferlin-null (Dysf<sup>-/-</sup>) mice exhibiting minor muscle damage and weakness without dramatic ambulatory dysfunction.