InterPro domain: IPR028796

Tetratricopeptide repeat protein 8 (TTC8, also known as BBS8) is part of the BBSome complex (BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10), which is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia [ 1 ]. The ciliary trafficking function of the BBSome is regulated by LZTFL1 (Leucine-zipper transcription factor-like 1) [ 2 ].

Primary cilia are ubiquitous cellular appendages that provide important sensory and signalling functions and their dysfunction underlies numerous human genetic disorders. The proteins disrupted in the human ciliary disorder Bardet-Biedl syndrome (BBS) are required for the localisation of G protein-coupled receptors to primary cilia on central neurons. The alteration of signalling caused by mislocalisation of ciliary signalling proteins underlies the BBS phenotype [ 3 ]. BBS8 is one of the genes involved in BBS. A splice-site mutation in TTC8/BBS8 is also known to cause nonsyndromic retinitis pigmentosa (RP) [ 4 ].

1. A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129, 1201-13
2. A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened. PLoS Genet. 7, e1002358
3. Bardet-Biedl syndrome proteins are required for the localization of G protein-coupled receptors to primary cilia. Proc. Natl. Acad. Sci. U.S.A. 105, 4242-6
4. A splice-site mutation in a retina-specific exon of BBS8 causes nonsyndromic retinitis pigmentosa. Am. J. Hum. Genet. 86, 805-12