The present invention relates to the identification of a gene, mutated at the most common locus now designated BBS1, that is involved in the genetic disease Bardet Biedl Syndrome (BBS), which is characterized by such diverse symptoms as obesity, diabetes, hypogonadism, mental retardation, renal cancer and other renal abnormalities, retinopathy and polydactyly or limb deformities. The human BBS1 protein disclosed herein is composed of 17 exons and spans approximately 23 kb. Methods of use for the gene, for example in diagnosis and therapy of BBS and in drug screening, also are described.