The number of coding genes is specific and limited in each individual species, and thus to increase the repertoire of proteins required for efficient and effective cellular activity, cells developed several molecular mechanisms to address this issue. 1 Transcriptional control is one such common mechanism where alternative splicing takes advantage of the fact that within a single given gene, intronic sequences can be regarded as exonic coding sequences. 2 Another mechanism involves posttranslational modifications that permit the generation of protein families encoded by a single gene. 3 The p53 tumor suppressor that was regarded for a long time as single protein, is encoded by one functional gene and was shown to be involved in a broad range of cellular activities. 4 As p53 is a transcription factor, 5 it is well possible that it can transactivate a family of individual specific target genes that are associated with a variety of functional pathways in the cell. Increasing the repertoire of the p53 protein types by alternative splicing is another anticipated mechanism. 6 Indeed, in the mouse model, an alternative spliced p53 mRNA form that is shorter in size and represents an altered C0-terminus was described. 7, 8 The latter exhibited an augmented DNA binding activity. 9 However, the lack of indications of such an analogous p53 molecule in humans made researches neglecting this mouse-specific issue. Interestingly, however, searching for p53 functionally and structurally related proteins led to the identification of families of protein members such as p63 and p73 as well as a variety of isoforms that are generated by diverse mechanisms in individual cell types under defined conditions. 10 As wild-type p53 has diverse functionalities in regulating cell growth, cell death, DNA repair, differentiation, development and more, and it is a key player in cancer development, 4 it is reasonable to speculate that such a nature of activities may be mediated by multiple p53 protein molecules. Indeed, p53 isoforms were found to regulate its tumor-suppressive functions, and their dysregulation was found in many cancers. 11