Yippee-like 3 (YPEL3) was reported in 2004 as one of five family members of the Yippee protein with conservation in species down to slime molds. While reports of other YPEL family members have surfaced our laboratory was the first to report that YPEL3 is induced by the p53 tumor suppressor. Furthermore we demonstrated that YPEL3 is growth suppressive, triggering cellular senescence in human cell lines and is down-regulated in several human tumors. Studies with mouse YPEL3, originally named small unstable apoptotic protein (SUAP), confirmed that the gene encodes a growth suppressive highly unstable protein. In this review we show that transcriptionally active forms of p73 and p63, family members of p53, can transactivate the human YPEL3 gene. While there are several reported YPEL3 transcripts and potentially 2 protein isoforms, no clear protein structure has been reported. As evidence mounts that YPEL3 is a tumor suppressor gene, studies aimed at understanding its biological function, regulation of gene expression and impact on tumorigenesis will help.