The Ly-6/uPAR proteins are a subfamily of urokinase-type plasminogen activator receptors (uPAR) characterized by a distinct disulfide bonding pattern between 8 or 10 cysteine residues and by a conserved pattern CCXXXXCN. The Ly-6/uPAR family can be further subdivided based on the presence or absence of a GPI-anchoring signal sequence. Ly-6/uPAR proteins attached to the cell membrane by a carboxy-terminal linker include Lynx-1 whereas secreted proteins include secreted mammalian Ly-6/uPAR-related protein 1 (SLURP-1) and SLURP-2, which is an isoform of Lynx-1. The amino acid sequence of SLURP-1 has some homology with the secreted snake α-neurotoxins, suggesting that its 3-dimentional structure may also be similar. Mutations in the gene coding for SLURP-1 in humans have been reported in individuals suffering from Mal de Meleda, a rare autosomal recessive skin disorder, characterised by hyperkeratosis on the palms of the hands and soles of the feet. Snake α-neurotoxins are known to interact with the muscle and neuronal subtypes of the nicotinic acetylcholine receptor (nAChR). α7 nAChRs have been reported to be involved in homeostasis and differentiation of epidermal keratinocytes. We assessed the effect of SLURP-1 at human α7 nAChRs expressed in Xenopus oocytes. Preincubation with SLURP-1 increased the amplitude of the ACh-evoked currents in a concentration dependent manner suggesting that SLURP-1 may exert its effects in vivo, via nAChRs where it acts as a signal in normal growth and development of keratinocytes. Mutations in the gene coding for SLURP-1, such as frame shift or introduction of a stop codon are expected to disrupt this action.