The CSTB gene encodes a small protein called stefin B (also called cystatin B) that is a member of the superfamily of cysteine protease inhibitors. Cystatin B functions as an intracellular thiol protease inhibitor of several papain-family cysteine proteases, cathepsins, which are lysosomal enzymes. The protein is thought to play a role in protecting against the proteases leaking from lysosomes.

The CSTB gene is located on the long arm of chromosome 21 at 21q22.3 and spans 3.0 kb of genomic DNA with a coding sequence consisting of three exons. Cystatin B is a ubiquitously expressed 98-amino acid protein and has a molecular weight of 11 kd.

CSTB is the only gene known to be associated with Unverricht-Lundborg disease. All but one affected individuals with this disease have been identified to have an unstable expansion of a 12-nucleotide (dodecamer) repeat 5prime-CCC-CGC-CCC-GCG-3prime in the promoter region in at least one of the two mutated CSTB alleles. The majority of affected individuals have this repeat on both alleles. Normal individuals have 2-3 repeats of dodecamer sequence, but most affected individuals have more than 30 repeats of this sequence in both alleles of the CSTB gene. This mutation accounts for approximately 90% of Unverricht-Lundborg disease alleles found throughout the world, and 99% of affected Finnish individuals have two disease-causing dodecamer expansions.

Nine other CSTB mutations have been identified as a compound heterozygous with dodecamer repeat expiation mutation in a small number of affected individuals. The c.10G>C mutation is the only mutation reported that does not occur in a compound heterozygous form with the dodecamer repeat expansion mutation.