MLL gene at human chromosome 11q23.3 is frequently rearranged or amplified in hematological malignancies, while PHLDB1, BCL9L, FOXN5 (FOXR1), RNF26, and MFRP genes linked to MLL gene are deleted in neuroblastoma. Here, we characterized the TMEM24 gene family by using bioinformatics. KIAA0285 gene within the 11q23.3 commonly deleted region of neuroblastoma was designated TMEM24, because KIAA0285 gene product was a 707-aa (or 706-aa) protein with N-terminal short cytoplasmic region, single transmembrane domain, and C-terminal large extracellular region. C21orf25 (NM_199050.1) encoded an N-terminally truncated 541-aa protein homologous to TMEM24. Complete coding sequence of C21orf25 was determined by assembling exons 1 and 2 within human genome sequence AP001745 and NM_199050.1 cDNA. Full-length C21orf25 encoded a 696-aa TMEM24-related protein with similar membrane topology. Exon-intron structure was conserved between TMEM24 and C21orf25 genes. TMEM24-ABCG4 locus at human chromosome 11q23.3 and C21orf25-ABCG1 locus at human chromosome 21q22.3 were paralogous regions (paralogons) with insertions of other genes due to recombination during evolution. Mouse 1300006O23 (BC060156.1) and 5830404H04 (NM_174847.1) cDNAs were derived from orthologs of human TMEM24 and C21orf25 genes, respectively. TMEM24 homologous domains (TM24H1 and TM24H2) were identified as novel domains conserved among TMEM24, C21orf25, 1300006O23, and 5830404H04. Human TMEM24, C21orf25 and their mouse homologs were type II transmembrane proteins with extracellular TM24H1 and TM24H2 domains. This is the first report on identification and characterization of the TMEM24 family.