Recently, the RCAN3 inhibitory role on human umbilical vein endothelial cells proliferation, both basally and under vascular endothelial growth factor or phorbol 12-myristate 13-acetate stimulation conditions, has been demonstrated. This process is probably mediated by calcineurin signalling and independent from the inflammatory and angiogenic processes. Moreover, we demonstrated that RCAN3 also interacts with TNNI3, the human inhibitory cardiac troponin that prevents contraction in the absence of calcium and troponin C. RCAN3 exon 2 product has been found to be sufficient for binding TNNI3. RCAN3 is the most recently identified member of the human RCAN gene family, appearing only in vertebrates, in agreement with the fact that the number of RCAN members tends to increase in more complex organisms. RCAN3 gene is localized on chromosome 1, it is composed of five exons and the coding sequence, included between exon 2 and exon 5, encodes for a 241 amino acid predicted protein, which shares a highly conserved consensus motif, known as the FLISPP motif, comprising the signature of the family. Since preliminary bioinformatic data revealed a not yet investigated major complexity of the human RCAN3 locus, an accurate multiple approach analysis of the locus was considered necessary. Our findings bear out possibility that gene expression regulation in higher eukaryotes is enriched with the wide number of alternative spliced isoforms, with data on overlapping sequences, sequences related to ncRNA and natural antisense RNA, whose presence at a gene locus identify a “multi-transcript’’ locus. It has been estimated that 40-60% of all human genes and 74% of multiexon human genes are alternatively spliced. These estimates do not take into account how many different alternatively spliced isoforms exist for any given gene. Different mechanisms of alternative splicing could be identified in human genes, from lacking three bases from one exon, like in subtle splicing, to lacking one or more discrete exons, like in our cases. All these mechanisms probably explain the functional complexity of vertebrates, as opposed to invertebrates. Among various molecular and cellular dysfunctions originated from mutations to HTT gene, which eventually lead to neuronal loss from striatal regions in HD patients, transcriptional deregulation is considered to be one of the important events. It has been proposed on the basis of theoretical analysis that as many as 30% of genes in the human genome may be the targets of miRNAs. However, latter estimates predict that as large as 90% of human genes are targets of miRNAs, although experimentally validated targets are limited. MiRNA genes are regulated in similar way as that of coding genes. For example, p53 is known to increase as well as decrease the expression of several miRNAs. Interestingly, p53 is one of the targets of miR-125b, which is itself negatively regulated by p53. RelA/NFkB regulates the expression of miR-146a. However, there is a report, which suggests for an activation of the transcription factor NFkB in response to apoptosis induced by p53. Besides, RelA/NFkB is also known to regulate p53 expression in tumor cells in response to hypoxia. All these results show that p53 directly or indirectly regulates RelA/NFkB expression and activity of NFkB and thus the expression of miR-146a. The other possibility of direct interference of p53 on miR-146a expression could not be ruled out and requires further studies. Even though it is conceivable that p53 can modulate the activity of NFkB, how the expression of RelA/NFkB is compromised remains unknown.