Microbes that thrive in extreme environments have tremendous potential for use in industry.  Many extremophiles are classified to Archaea, one of the least characterized domains in terms of metabolic and regulatory networks.  Based on our work, we find proteases, such as proteasomes, are important in controlling the quality and regulated turnover of proteins within these networks.  Using Haloferax volcanii as a model, we demonstrate that the 20S proteasomal core particle is essential for growth of this halophilic archaeon.  In addition, proteasomes were found to be important for survival under stressful conditions (e.g., growth in the presence of L-canavanine, low salt).  The regulatory ATPase particles of proteasomes (PanA and PanB) were required for carotenoid production and influenced phosphoproteome composition.  Over 100 putative proteasomal substrates were identified using various methods of phosphopeptide and phosphoprotein enrichment coupled with multidimensional protein identification technology (MudPIT), 2D-PAGE, and tandem mass spectrometry (ESI-QTOF and LTQ linear ion trap MS/MS).  Many of the (phospho)proteins identified as differential in protesome-deficient vs. wild type cells are predicted to function in phosphate assimilation, polyphosphate biosynthesis, translation, cell division, DNA replication and repair, protein phosphorylation, signal transduction, and central metabolism.  The half-lives of several of these differential proteins were analyzed by pulse-chase and found to be significantly enhanced in proteasome mutant compared to parent strains.  Overall, our studies demonstrate that the combined use of global methods (e.g., proteomics) with traditional biochemical approaches has and will continue to provide greater insight into the role proteasomes play in the Archaea.