The inability to remove protein aggregates in non-dividing cells such as neurons or muscles is a key factor in the development and progression of neurodegenerative diseases and myopathies. While protein aggregation diseases share common features, a single mechanism cannot explain the molecular-level events that culminate in abnormal protein accumulation. A hallmark of protein aggregate diseases is the accumulation of specific proteins, suggesting that proteins susceptible to in vivo aggregation share common structural characteristics and/or biological functions. In protein aggregation diseases affecting muscle, a general theme has emerged in which aggregated proteins and organelles accumulate in regions, excluding normal muscle proteins. However, the cellular and/or mechanical triggers that initiate and prevent the clearance of protein aggregates and cause eventual myofibrillar dissolution are unclear. Using Drosophila as a model system, we have identified the conserved serine/threonine kinase NUAK as essential in promoting the autophagic clearance of protein aggregates. Proteomic and genetic approaches are currently being used to decipher the role of NUAK and associated proteins during protein turnover, especially in response to mechanical tension.