The coordination of sensing and responding to cell wall stress is crucial for fungi, and precise temporal control of cell wall stress response regulators underpins the rapid mobilization of signaling cascades that govern cellular integrity. We demonstrated that Cas5 not only becomes activated in response to cell wall stress but it also maintains cell wall stability under basal conditions (Figs. 3 and 5). Although Cas5 is not broadly conserved in the fungal kingdom, its activation is regulated by a conserved protein phosphatase, Glc7, which has 91% protein identity to the S. cerevisiae ortholog. In S. cerevisiae, temperature sensitive glc7 mutants exhibit sorbitol-remediable lysis defects at the restrictive temperature, due to impaired cell wall integrity43. We demonstrated Glc7 is required for cell wall maintenance in C. albicans (Fig. 7). Glc7 substrates in S. cerevisiae include three proteins with sequence similarity to Cas5: Mig1, Msn2, and Msn4. Msn2 and Msn4 are transcription factors that are required for general stress response in S. cerevisiae, but not in C. albicans 50, 51. This highlights a divergence in signal transduction cascades required to respond to environmental stressors, and suggests that Cas5 may be the central downstream effector of Glc7 that modulates stress responses in C. albicans. Consistent with this possibility, Cas5 controls responses not only to cell wall stress, but also to cell membrane stress exerted by the azole antifungal drugs52.