Intersectin, which is also designated Ese1 or ITSN1, is a component of the cellular endocytic machinery. Intersectin is composed of two N-terminal Ese15 homology (EH) domains, a central highly charged region and five C-terminal SH3 domains, which all largely contribute to the association of Intersectin with other components of the endocytic pathway. The EH domain is particularly responsible for the directed localization of Intersectin to Clathrin-coated pits near the plasma membrane. Within the endocytic vesicles the SH3 domains facilitate the binding of Intersectin with Dynamin, and the central domain is essential for the association of Intersectin with SNAP 25. Two isoforms of Intersectin are produced as a result of alternative splicing in a stop codon, and they are designated as Intersectin-short and long (or IntersectinS and IntersectinL) to reflect an extended C-terminal domain. The long form, which has an extended C-terminal domain, is specifically expressed in neurons; the short form is detected in both glial and nonneuronal cells. The related proteins Intersectin-2 and the murine homolog Ese2 also contain the characteristic N-terminal EH domains, the central coiled-coil domain and five C-terminal SH3 domains and are likely involved the endocytic scaffolding complexes.