Dominant-negative disease-causing mutations in the human caveolin genes (Cav-1 and Cav-3). Sequence alignment of all the known caveolins indicates that most of the disease-causing mutations found in human caveolin-3 (R26Q, ΔTFT, and P104L; LGMD-1C) and human caveolin-1 (P132L; breast cancer) coincide with one of the twelve residues (demarcated by boxes) that are conserved in all caveolins from worms (C. elegans) to humans. Interestingly, many of these mutations seem to act in a dominant-negative fashion by mis-localizing or causing the degradation of the wild-type caveolin proteins. Note that the mutations, Cav-1 (P132L) and Cav-3 (P104L), are analogous (see asterisk). LGMD-1C, limb-girdle muscular dystrophy, type 1c.