Synaptojanin-2 is a ubiquitously expressed inositol polyphosphate 5-phosphatase. The longest deduced protein, designated Synj2-alpha, contains 1,216 amino acids and has a calculated molecular mass of 140 kD. Synj2 contains an N-terminal Sac1 (SACM1L) homology domain, a central inositol 5-prime-phosphatase domain, and a C-terminal proline-rich region. Synj2 variants arise from the use of 2 possible initiation sites and at least 6 different exons encoding C-terminal domains. Initiation from the alternative start sites results in isoforms that vary in the presence of 84 amino acids in the N-terminal part of the Sac1 homology domain. Database analysis indicated the presence of a third putative initiation site in human SYNJ2, resulting in a protein that lacks most of the Sac1 homology domain.