We have determined the structure of the human laminin gamma 2 chain gene (LAMC2), which is mutated in some patients with junctional epidermolysis bullosa. Eight lambda phage clones isolated from a genomic library and three subgenomic lambda phage clones made from a plasmid artificial chromosome clone spanned 75 kb, including the 55-kb gene. The LAMC2 gene contains 23 exons and is structurally highly homologous with the 28-exon LAMC1 gene (Kallunki et al., 1991, J. Biol. Chem. 266: 221-228), with 16 exons having identical sizes in the two genes. The gene analysis demonstrated that two previously described different size gamma 2 chain cDNAs (Kallunki et al., 1992, J. Cell Biol. 119: 679-693) are the result of alternative splicing. The longer gamma 2 chain is formed by using the coding sequence of the last exon 23, while the shorter gamma 2* chain is formed by using only 22 exons, together with part of the 5' end of intron 22. The two mRNAs were shown to have different expression patterns in 17-week-old human embryonic tissues, with the longer gamma 2 chain transcript strongly expressed in epithelia of all tissues studied, while distinct expression of the shorter gamma 2* chain mRNA was observed only in the cerebral cortex, in lung, and in distal tubules of the kidney.