Intriguingly, activation of PKG pharmacologically (PDE5 inhibitor, sildenafil) or genetically (expression of a constitutively active PKG) in a proteinopathy model (CryABR120G) reduced the accumulation of ubiquitinated proteins and cleared the degradation of misfolded, but not normal, proteins (Ranek et al., 2013). The gene discussed is PDE5A; the disease is proteostasis deficiencies.