SHIP2, also known as 'phosphatidylinositol-3,4,5-trisphosphate 5-phosphatase 2,' is a cytoplasmic protein that translocates to membrane ruffles when activated, due to different stimulus and cell type. It belongs to the inositol-1,4,5-trisphosphate 5-phosphatase family with a SAM (sterile alpha motif) domain and a SH2 domain. SHIP2 specifically hydrolyzes the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3) to produce PtdIns(3,4)P2, thereby negatively regulating the PI3K (phosphoinositide 3-kinase) pathways and also in regulating PI3K-dependent insulin signaling, EGF signaling pathway and a signaling pathway that regulates actin cytoskeleton remodeling. SHIP2 is required for the maintenance and dynamic remodeling of actin structures as well as in endocytosis, having a major impact on ligand-induced EGFR internalization and degradation. It regulates cell adhesion, cell spreading and neuritogenesis and acts as a negative regulator of EPHA2 receptor endocytosis and of the FC-gamma-RIIA receptor (FCGR2A). SHIP2 mediates signaling from the FC-gamma-RIIB receptor (FCGR2B), playing a central role in terminating signal transduction from activating immune/hematopoietic cell receptor systems. Expression is widely seen in most tissues but primarily in skeletal muscle, heart, brain and transformed myeloid cells and in primary macrophages, but not in peripheral blood monocytes.