A cDNA encoding a novel member of the S-lectin family has been cloned from human epidermis. The 14-kDa protein of pI 7 predicted by the 136-amino-acid open reading frame of the sequence was called galectin-7 according to the presently accepted nomenclature. A GST fusion protein authentified the lactose-binding properties expected for a member of this lectin subfamily. Galectin-7 was identified on two-dimensional gels of keratinocyte protein extracts. Differential and in situ hybridizations indicate that this lectin is specifically expressed in keratinocytes. It is expressed at all stages of epidermal differentiation (i.e., in basal and suprabasal layers). It is moderately repressed by retinoic acid, a behavior contrasting with those of other keratinocyte markers sensitive to this agent, which, either basal, are induced, or suprabasal, are repressed. This effect of retinoic acid on a keratinocyte cell type marker such as galectin-7 is more reminiscent of its metaplasiogenic effect in vivo than of its inhibitory effect on terminal epidermal differentiation in vitro. This interpretation is supported by the fact that in chick epidermis a 14-kDa S-lectin is suppressed during retinoic acid-induced mucous metaplasia.