Inositol molecules phosphorylated with mono- and di-phosphates (IPs and PP-IPs respectively) perform multiple key functions in eukaryotes. However, their role in fungal pathogens has never been addressed. We investigate IP/PP-IP biosynthesis pathway in a model pathogenic fungus, Cryptococcus neoformans, which causes life-threatening meningoencephalitis. Phenotypic analysis of IP and PP-IP-deficient mutants combined with gene expression profiling identifies IP₇ (PP-IP₅) generated by the IP₆ kinase Kcs1 as a key signaling molecule in C. neoformans. Absence of this crucial metabolite affects cell wall integrity, melanization, mating and virulence in wax moth and murine models of cryptococcosis. IP₇-deficient (Δkcs1 mutant) cells fail to be recognized and internalized by monocytic THP1 cells and blood-derived monocytes, as compared to WT C. neoformans. At the gene expression level, the absence of IP₇ leads to elevated expression of protein biosynthesis machinery and reduced expression of genes encoding enzymes of citric acid and glyoxylate cycles, fatty acid β-oxidation pathway and gluconeogenesis. Furthermore, expression of multiple genes encoding transmembranal proteins, particularly sugar transporters, and secreted proteolytic enzymes is lower in Δkcs1, as compared to wild type. Taken together, our findings establish Kcs1-generated IP₇ as a major regulator of cellular metabolism affecting nutrient acquisition and surface properties of the fungal cell, and therefore crucially important for host-fungus interaction and virulence.