Smad Interacting Protein 1 (SIP1) is observed in neural crest derived cells (peripheric nervous system, enteric nervous system, facial neurectoderm and cranial nerve ganglia), central nervous system, genital tubercle, muscles and kidneys in the developing human. SIP1 belongs to the delta-EF1/Zfh1 family of 2-handed zinc finger/homeodomain proteins and contains a SMAD-binding domain, a homeodomain and two clusters of zinc fingers on the N- and C-termini. SIP1 can be induced by TGF. SIP1 plays a crucial role in normal embryonic development of neural structures and the neural crest. Mutations in the SIP1 gene cause a form of Hirschsprung disease (HSCR). Patients with SIP1 mutations show mental retardation, delayed motor development, epilepsy, microcephaly, distinct facial features and/or congenital heart disease. SIP1 is also involved in the regulation of epithelial to mesenchymal transition, an important process in tumor progression.