Three lines of defense against misfolded proteins. There are three protective mechanisms that are involved in minimizing the toxicity of misfolded proteins: proteasomal degradation (I), macroautophagic clearance (II), and inclusion body formation (III). Ubiquitin is linked to each of these processes, as it can target proteins for proteasomal and macroautophagosomal degradation and is enriched in inclusion bodies.