The ubiquitin-proteasome system (UPS) is the major intracellular degradation 
system, and its proper function is critical to the health and function of 
cardiac cells. Alterations in cardiac proteasomes have been linked to several 
pathological phenotypes, including cardiomyopathies, ischemia-reperfusion 
injury, heart failure, and hypertrophy. Defects in proteasome-dependent cellular 
protein homeostasis can be causal for the initiation and progression of certain 
cardiovascular diseases. Emerging evidence suggests that the UPS can 
specifically target proteins that govern pathological signaling pathways for 
degradation, thus altering downstream effectors and disease outcomes. 
Alterations in UPS-substrate interactions in disease occur, in part, due to 
direct modifications of 19S, 11S or 20S proteasome subunits. Post-translational 
modifications (PTMs) are one facet of this proteasomal regulation, with over 400 
known phosphorylation sites, over 500 ubiquitination sites and 83 internal 
lysine acetylation sites, as well as multiple sites for caspase cleavage, 
glycosylation (such as O-GlcNAc modification), methylation, nitrosylation, 
oxidation, and SUMOylation. Changes in cardiac proteasome PTMs, which occur in 
ischemia and cardiomyopathies, are associated with changes in proteasome 
activity and proteasome assembly; however several features of this regulation 
remain to be explored. In this review, we focus on how some of the less common 
PTMs affect proteasome function and alter cellular protein homeostasis. This 
article is part of a Special Issue entitled "Protein Quality Control, the 
Ubiquitin Proteasome System, and Autophagy".