In mammals, Ins(1,4,5)P3, the well known calcium mobilization messenger, is phosphorylated in the cytosol at the 3-position of the inositol ring to yield Ins(1,3,4,5)P4 by Ins(1,4,5)P3 3-kinases A, B and C isoforms as well as by inositol polyphosphate multikinase (Ipmk). Studies in gene-deficient mice have revealed that these enzymes and Ins(1,3,4,5)P4, their reaction product, play essential role in multiple physiological processes, ranging from synaptic plasticity, hematopoietic cell survival, development and function, to mRNA export, transcriptional regulation and chromatin remodelling. Rather than to provide an unique and “universal” mechanism of Ins(1,3,4,5)P4 action, these studies in genetically-modified mice point for a role of this inositide in the control of calcium mobilization, of the subcellular localisation of PH domain-containing target proteins, and of higher inositol phosphate production. Mice deficient for the B isoform of inositol 1,4,5-trisphosphate 3-kinase (Itpkb) develop profound alterations in T and B cells as well as in neutrophils and mast cells. Our recent studies indicate that the 3-kinase Itpkb and Ins(1,3,4,5)P4 are important for the survival of naïve mature B cells and the control of proapoptotic Bim protein expression, rather than for the control of B cell transition from one developmental stage to another. They also suggest that Itpkb is an important component in the control of B cell anergy.