Both isoforms of CEACAM1 are down-regulated in epithelial cancers arising in the liver, prostate, bladder and colon [6, 7, 8, 9, 10, 11, 12] , a finding that prompted re-expression analysis aimed at defining structure and function relationships. Restoration of expression by infecting rat cell lines derived from primary hepatocellular carcinomas (r-HCC) with a CEACAM1-4L retrovirus resulted in potent growth suppression in vitro and tumor suppression in vivo [13] . Further analysis showed that the 4L cytoplasmic domain was necessary and sufficient for tumor suppression [14] , an activity that required phosphorylation of serine 503 and in colon carcinoma cells, concurrent phosphorylation of tyrosine 488 [15, 16] .