We have cloned a new member of a family of mammalian proteins homologous to Sec22p, a v-SNARE in Saccharomyces cerevisiae required for transport between the endoplasmic reticulum (ER) and the Golgi apparatus. The open reading frame encodes a polypeptide of 250 amino acids which is homologous to, but obviously different from, the recently reported mammalian Sec22p homologs rat sec22a, mouse sec22b, and hamster ERS-24. Northern blot analysis revealed two transcripts of about 1 and 5 kb respectively which are ubiquitously expressed. myc-epitope tagged sec22c is localized to the ER. Overexpression of the myc-tagged protein resulted in an anomalous staining pattern of SNARE molecules participating in ER-Golgi transport such as syntaxin 5 and mammalian bet1, but not the endosomal SNARE syntaxin 7. The presence of multiple forms of sec22 protein in the mammalian early secretory pathway is in-line with task specification in a highly elaborate transport machinery.