CPEB4 gene covers 71.98 kb on human chromosome 5 (5q35.2), between 173315331 and 173387313 (according to hg19-Feb_2009, UCSC).

The mRNA of CPEB4 contains 10 exons and 9 introns. Multiple transcript variants encoding different isoforms (10 splice variants) have been found for this gene.

CPEB4 is a RNA binding protein that belongs to the CPEB-family of proteins. In vertebrates, 4 members (CPEB1, CPEB2, CPEB3, CPEB4) have been identified, CPEBs2-4 are closely related whereas CPEB1 is the most distant member of the family (Wang et al., 2010). All members have a conserved carboxy-terminal region, composed of two RNA Recognition motifs (RRM) and two zinc-finger-like motifs (Hake et al., 1998), and a regulatory highly variable N-terminal domain.
10 different isoforms have been described for CPEB4:
- Isoform a: 729 amino acids, 80.2 kDa protein, RRM motifs: aa 472-563 and aa 580-662.
- Isoform b: Exon 3 skipped, 712 amino acids, 78.3 kDa protein.
- Isoform c: Exon 3 and 4 skipped, 704 amino acids, 77.3 kDa protein.
- Isoform d: Exons 3, 4 and 9 skipped, 639 amino acids, 69.8 kDa protein.
- Isoform e: Exons 3, 4, 5, 6, 7, 8, 9 and 10 skipped, 389 amino acids, 43.1 KDa protein.
- Isoform f: Exons 1 and 4 skipped, 339 amino acids, 38 kDa protein.
- Isoform g: Exons 1, 3 and 4 skipped, 322 amino acids, 36.2 kDa protein.
- Isoform h: Exons 1, 2, 3 and 4 skipped, 295 amino acids, 33 KDa protein.
- Isoform i: Exons 1 (partly) 3, 4, 5, 6, 7, 8, 9 and 10 skipped, 226 amino acids, 25.3 KDa protein.
- Isoform j: Exons 1 (partly) 4, 6, 7, 8, 9 and 10 skipped, 146 amino acids, 16.3 kDa protein.

CPEBs are widely expressed in different mammalian tissues and tumours and sometimes with overlapping patterns. CPEB4 mRNA is highly expressed in embryonic stages (E14.5) brain, heart, kidney and lung. Moreover, a lower expression is also present in liver, spleen and ovary (Fernandez-Miranda et al., 2012). At protein level, an upregulation in Pancreatic Ductal Adenocarcinoma (PDA) and glioblastoma (Ortiz-Zapater et al., 2011) has also been described. At RNA level, CPEB4 misregulation is present in several types of cancer: prostate, breast, skin, lung, brain and digestive apparatus (DAmbrogio et al., 2013) but this misregulation requires further characterization because CPEB4 mRNA is under a strong post-transcriptional regulation.

Cytoplasmic Polyadenylation Element Binding protein 4 (CPEB4) is mostly cytosolic, however it has been reported that it can be a nucleus-cytoplasm shuttling protein in neurons, in response to calcium-mediated signalling. In fact, CPEB4 becomes nuclear in response to focal ischemia and when cultured neurons are deprived of oxygen and glucose (Kan et al., 2010).

CPEBs are RNA binding proteins that recognize cis-acting elements named Cytoplasmic Polyadenylation Element (CPE), that are located in the 3UTR of some mRNAs. They were originally described in Xenopus laevis oocytes, where they control translation of maternal mRNAs during meiosis by regulation of the length of the polyA tail (Hake and Richter, 1994). However, these proteins can be also found in other non-germ cells suggesting other functions for CPEBs (Costa-Mattioli et al., 2009; Mendez and Richter, 2001; Richter, 2007). CPEB4 recognizes the same CPE as CPEB1, although with less affinity (Novoa et al., 2010; Igea et al., 2010). In oocytes, CPEB4 is required for meiotic progression between MI and MII and regulates CSF arrest (Igea et al., 2010). In somatic cells, CPEB4, together with CPEB, regulates mitotic poly(A) tail elongation and is required for cell proliferation (Novoa et al., 2010). Moreover, CPEB4 also plays a role in cancer where overexpression of CPEB4 correlates with increased malignancy, tumour growth and vascularization in pancreatic cancer and glioblastoma (Ortiz-Zapater et al., 2011), suggesting that overexpression of CPEB4 can be a general mechanism in cancer development and that CPEB4 could behave as an oncogene.

CPEB4 orthologs are also present in other species, such as Mus musculus (Cpeb4), Xenopus laevis (cpeb4), Danio rerio (cpeb4), Drosophila melanogaster (Orb2) and Caenorhabditis elegans (cpb1-2).

Relevant point mutations have been described for other members of the CPEB family, such as the point mutation T>C in exon 3 of the CPEB3 mRNA (rs11186856), which has been associated with a reduced translation efficiency and impaired episodic memory (Vogler et al., 2009). However, even though there are some point mutations described for CPEB4, up to date none of them have been proved to have a functional relevance.