Plant vacuolar transporters, particularly CAX (Cation/H+ Exchangers) responsible for Ca2+/H+ exchange on the vacuole tonoplast, play a central role in governing cellular pH, ion balance, nutrient storage, metal accumulation, and stress responses. Furthermore, CAX variants have been employed to enhance the calcium content of crops, contributing to biofortification efforts. Recent research has uncovered the broader significance of these transporters in plant signal transduction and element partitioning. The use of genetically encoded Ca2+ sensors has begun to highlight the crucial role of CAX isoforms in generating cytosolic Ca2+ signals, underscoring their function as pivotal hubs in diverse environmental and developmental signalling networks. Interestingly, it has been observed that the loss of CAX function can be advantageous in specific stress conditions, both for biotic and abiotic stressors. Determining the optimal timing and approach for modulating the expression of CAX is a critical concern. In the future, strategically manipulating the temporal loss of CAX function in agriculturally important crops holds promise to bolster plant immunity, enhance cold tolerance, and fortify resilience against one of agriculture's most significant challenges, namely flooding.