We describe the isolation and characterization of a full-length cDNA encoded by a gene that was significantly down-regulated in the affected skin of patients with psoriasis vulgaris. The cDNA was isolated from a keratinocyte cDNA library and its sequence was found to correspond to a hypothetical locus recorded in GenBank with the accession number . The nucleotide sequence of the full-length cDNA was found to have an open reading frame of 1365 amino acids and to span approximately 12 kb of genomic DNA with 39 exons on chromosome 16q22. The deduced amino acid sequence contains four distinct structural regions, an RGD motif, a leucine-rich repeat (LRR) region, a tropomodulin domain, and a proline-rich domain. The gene was consequently designated as RLTPR (RGD, leucine-rich repeat, tropomodulin and proline-rich containing protein). The RLTPR hypothetical protein has a functional domain organization similar to Acan125, a myosin-binding protein expressed by Acanthamoeba castellanni. RT-PCR with RLTPR PCR primers amplified products from cDNAs prepared from all of the 30 different tissues that we examined including thymus, spleen, colon, skin, skin keratinocytes, skin fibroblasts and fetal skin. During the course of screening the human keratinocyte cDNA library, some alternative splicing was also detected in three regions of the RLTPR gene. In addition, sequence analysis of the RLTPR genes from eight psoriasis patients and eight healthy controls revealed a number of synonymous and nonsynonymous SNPs that may be useful markers for future disease association studies.