Adapter protein that may provide indirect link between the endocytic membrane traffic and the actin assembly machinery. May regulate the formation of clathrin-coated vesicles (CCPs). Seems to be involved in CCPs maturation including invagination or budding. Involved in endocytosis of integrin beta-1 (ITGB1) and transferrin receptor (TFR). Plays a role in dendrite formation by melanocytes (PubMed:23999003). Belongs to a complex that may contain multimers of ITSN1, ITSN2 and EPS15, and different partners according to the step in the endocytic process. Interacts with ADAM15. Interacts with FASLG. Interacts with ANKRD54 (By similarity). Interacts with FCHO2. (Microbial infection) Interacts with herpes virus 8 protein K15. Additional isoforms seem to exist. Expressed in melanocytes (PubMed:23999003). Ubiquitous. Isoform 1 is primarily expressed in adult heart and liver. Overexpression results in the inhibition of the transferrin uptake and the blockage of the clathrin-mediated endocytosis. It is uncertain whether Met-1 or Met-2 is the initiator. Studies in clathrin-mediated endocytosis of ITGB1 and TFR used a siRNA mixture of ISTN1 and ISTN2 suggesting a partially overlapping role of the EH domain-containing proteins. Truncated N-terminus. Truncated N-terminus. Extended N-terminus. Extended N-terminus.