The invertebrate organisms Caenorhabditis elegans and Drosophila melanogaster express a single MCTP gene, whereas vertebrates express two MCTP genes (MCTP1 and MCTP2) whose primary transcripts are extensively alternatively spliced. Most of the MCTP sequences, in particular the C2 domains, are highly conserved. All MCTP C2 domains except for the second C2 domain of MCTP2 include a perfect Ca2+/phospholipid-binding consensus sequence. In higher eukaryotes, multiple C2 domain-containing transmembrane protein (MCTP2) is similar to Pex30: it contains an RHD and resides in ER domains where most nascent LD biogenesis occurs and that often associate with peroxisomes. The MCTP2 gene, located on chromosome 15q26, influences adiposity. The MCTP2 gene is involved in intercellular signal transduction and synapse function. MCTP2 is also a novel genetic cause of CoA and related cardiac malformations.