Flotillin-2/ESA (epidermal surface antigen) plays a role in intercellular epidermal adhesion. Epidermal surface proteins have an important role in normal epidermal maintenance and function. In addition, they are involved in various autoimmune diseases in which auto-antibodies bind to normal epidermal cell surface proteins. This binding causes cell disadherence that leads to blister formation. Such antibodies have been utilized to identify new proteins involved in epidermal cell adhesion. One of these antibodies, ECS-1, was used to isolate Flotillin-2/ESA. The single copy ESA gene is located on the long arm of human chromosome 17, in the region containing the gene for neurofibromatosis 1 (NF1). ESA mRNA is expressed in cultured keratinocytes, melanocytes, fibroblasts, and carcinoma and melanoma cell lines. Flotillin-2/ESA may play a critical role in epidermal structure and maintenance.