By microarray assay we identified ESTs (expressed sequence tags) whose expression was predominantly increased in the affected skin of patients with psoriasis vulgaris. Among them, a full-length cDNA sequence corresponding to one of those ESTs (AI829641) was isolated by screening of cultured human keratinocyte cDNA libraries. This cDNA encodes a novel member of the Ly-6/uPAR superfamily, designated SLURP-2 (secreted Ly-6/uPAR related protein 2). SLURP-2 has an open reading frame of 97 amino acids containing 10 conserved cysteine residues. SLURP-2 has a single functional copy within the LY6 superfamily gene cluster at chromosome 8q24.3. RT-PCR (reverse transcriptase-polymerase chain reaction) expression analysis revealed that SLURP-2 was expressed in multiple tissues, mainly in the epithelial cells including the skin and keratinocytes, but not in spleen or bone marrow. Comparison of the expression of this gene among the psoriatic lesional and nonlesional skin of patients and the normal skin of healthy individuals detected by quantitative real-time RT-PCR analysis disclosed that SLURP-2 was up-regulated threefold in psoriatic lesional skin. These findings suggest that SLURP-2 may be involved in the pathophysiology of psoriasis through its role in keratinocyte hyperproliferation and/or T cell differentiation/activation.