The inositol polyphosphate 4-phosphatases selectively remove the phosphate from the 4-position of various phosphatidylinositols, which generate second messengers in response to extracellular signals. Both the type I and type II 4-phosphatases catalyze the hydrolysis of phosphatidylinositol 3,4-bisphosphate, inositol 1,3,4-trisphosphate, and inositol 3,4-bisphosphate. Type I and type II 4-phosphatases are both alternatively spliced into two isoforms, a and b, which have been detected in human platelets, rat brain, heart, skeletal muscle and spleen; and all isoforms contain a conserved motif CKSAKDRT, which contains the active site consensus sequence C-X5-R. Both type I and II 4-phosphatases are thought to regulate the level of intracellular calcium by acting as signal terminating enzymes.