Next, we assessed if Cas5 regulates the expression of genes important for cell wall homeostasis in the absence of cell wall stress. We found that 110 out of the 275 genes that have reduced RNA PolII binding in the cas5Δ/cas5Δ mutant under basal conditions were associated with cell membrane, cell wall, and cell periphery GO components (Supplementary Data 1). Thus, we predicted Cas5 enables cell wall stability in the absence of cell wall stress, such that deletion of CAS5 would induce cell wall stress under basal conditions. To determine if a cas5Δ/cas5Δ mutant is intrinsically defective in cell wall architecture, we monitored phosphorylation of the terminal cell wall integrity MAP kinase, Mkc1, under basal conditions32. Compared with a wild-type control, the cas5Δ/cas5Δ mutant had elevated levels of Mkc1 phosphorylation under basal conditions (Fig. 3c and Supplementary Fig. 2a). Moreover, expression of RLM1, a transcription factor downstream of Mkc1, was upregulated in the cas5Δ/cas5Δ mutant under basal conditions (Fig. 3d), suggesting strains lacking Cas5 experience intrinsic cell wall stress. Our results indicate Cas5 maintains cell wall homeostasis under basal conditions and during cell wall stress.