The inositol polyphosphate 5-phosphatases selectively remove the phosphate from the 5-position of various phosphatidylinositols, which generate second messengers in response to extracellular signals. Synaptojanins are characterized by an N-terminal SAC1-like sequence, a central 5-phosphate domain, and a unique C-terminal sequence and have been shown to use phosphatidylinositol 4,5-bisphosphate as a substrate. Synaptojanins exist as two isoforms, synaptojanin 1 and 2, which differ in the C-terminal domain, and each isoform has multiple variants produced by alternative splicing. Synaptojanin 1 is expressed as two major forms: the shorter is found in brain while the longer is expressed in peripheral tissues. Eight splice variants of synaptojanin 2 have been detected, including a brain specific isoform. Synaptojanins are thought to participate in the endocytosis of synaptic vesicles and the regulation of the actin cytoskeleton.