The eukaryotic calcium/calmodulin-dependent protein phosphatase calcineurin is crucial for the environmental adaption of fungi. However, the mechanism of coordinate regulation of the response to salt stress by calcineurin and the high-affinity calcium channel CchA in fungi is not well understood. Here we show that the deletion of cchA suppresses the hyphal growth defects caused by the loss of calcineurin under salt stress in Aspergillus nidulans. Additionally, the hypersensitivity of the ⌬cnaA strain to extracellular calcium and cell-wall-damaging agents can be suppressed by cchA deletion. T o rapidly sense and respond to different environmental conditions, organisms have evolved signaling pathways to coordinate growth, proliferation, and metabolism (1-6). Among them, the calcium-mediated signaling pathway plays an important regulatory role in various physiological processes, such as cell cycle, cytoskeletal rearrangement, ion homeostasis, and stress response (7-10). Calcium homeostasis systems are highly regulated pathways used by cells to maintain cytoplasmic Ca 2ϩ concentrations ([Ca 2ϩ ] c )within an optimal range in the cytosol and other organelles (11)(12)(13)(14). The rise and fall of free [Ca 2ϩ ] c can be directly sensed, decoded, and retransmitted to cellular targets, such as the Ca 2ϩ /calmodulin-dependent protein phosphatase calcineurin, which is highly conserved from yeasts to humans and mediates many important cellular processes (15,16).Calcineurin is a member of the serine-threonine-specific protein phosphatase (PP) family. It differs from other phosphatases in its metal ion requirements, range of substrate specificity, and cellular regulation (17). Calcineurin exists as a heterodimer of catalytic subunits (CnA) and regulatory subunits (CnB) (18,19), and the CnA subunit contains the catalytic domain and three regulatory domains, including the CnB-binding, calmodulin-bind-