## 1 Introduction  
_Cryptococcus neoformans_ has significant clinical importance. This encapsulated yeast is responsible for causing cryptococcosis, a potentially life-threatening fungal infection, particularly in AIDS patients, organ transplant recipients, or those undergoing immunosuppressive therapies [1]. As an opportunistic pathogen, _C. neoformans_ exhibits a remarkable ability to respond to stress, such as high temperatures, high osmolarity, oxidative environments, nutrient abundance, and radiation, which are features intricately associated with its survival in nature but also associated with virulence in the host. The stress response depends on sophisticated cell signaling mechanisms that enable it to sense and respond to changes [2; 3; 4; 5]. Calcineurin is pivotal in orchestrating fungal signaling, acting as a central hub that modulates adaptation to various environmental challenges [6]. As a calcium-calmodulin-activated protein phosphatase, calcineurin regulates critical cellular processes in fungi, such as ion homeostasis, cell wall integrity, growth, virulence, drug resistance, and response to stresses [7]. Upon exposure to stress or antifungal agents, calcineurin, a heterodimer composed of catalytic (Cna1) and regulatory (Cnb1) subunits, becomes activated by calcium-calmodulin. This complex binds to the catalytic subunit, exposing the active site of the autoinhibitory domain at the C-terminus; the Cnb1 subunit is also a Ca\({}^{+}\)-binding protein and considered a calcium sensor [8]. The active calcineurin complex leads to the dephosphorylation of target proteins and subsequent alterations in gene expression patterns [9]. This activation aids fungi in maintaining cellular integrity and viability under adverse conditions [8]. The most well-characterized role of the calcineurin complex in _C. neoformans_ is in high-temperature growth at 37 \({}^{\circ}\)C [10; 11]. It has been shown that cell exposure to inhibitors of the calcineurin complex, such as cyclosporine A, or the deletion of the regulatory and catalytic subunits leads to high-temperature growth failure and virulence attenuation in animal models of infection [3; 12; 13]. The transcription factor Crz1/Sp1 has been identified as the main target of the complex during stress [14] in _C. neoformans_ and other fungi [6]. Calcineurin dephosphorylates Crz1 in the cytoplasm, which enters the nucleus to transcribe its target genes, leading to several cellular responses [15]. Crz1 has been found in stress granules (P-bodies), and Crz1 domains without previously attributed functions are linked to different localizations and functions [16]. However, the calcineurin complex has Crz1-independent roles: for example, [PERSON] et al. (2016) identified many calcineurin targets using a phosphoproteomic assay; besides Crz1, proteins involved in P-bodies/stress granules (PBs/SGs) were found as calcineurin substrates. Also, Cna1-Gfp co-localizes to PBs/SGs upon thermal stress, suggesting it may be involved in mRNA decay [17; 18]. These observations are evidence that calcineurin is involved in a myriad of molecular processes to overcome stress. For example, Cna1 and Cnb1 subunits were found in a protein complex with the Cys3 transcription factor, a major regulator of sulfur uptake and amino acid biosynthesis that localizes mainly to the nucleus [19]. Along the same lines, Cna1 physically interacts with Met3 (ATP sulfurylase), a cytoplasmic protein involved in the first committed step of the sulfur uptake pathway, suggesting that the calcineurin complex contributes to nutritional stress regulation at multiple steps of the pathway [20]. Earlier, [PERSON] et al. (2000) observed cationic stress sensitivity (Na\({}^{+}\) and Li\({}^{+}\)) in \(cna1\Delta\) mutants of _C. neoformans_; conversely, _C. deneoformans_ was not considered sensitive [10; 12]. Cna1 and Cnb1 interact physically with Gpp2, the glycerol phosphate phosphatase responsible for glycerol biosynthesis, which is required to counteract cationic stress and promote cell wall integrity in _C.