TTC8 is a core structural component of the BBSome, an octameric ciliary transport complex essential for protein sorting to primary cilia 1. As a tetratricopeptide repeat domain protein, TTC8 functions in BBSome assembly and ciliary localization, where it facilitates Rab8-mediated vesicle docking and fusion at the ciliary base to promote ciliary membrane extension 1. TTC8 also regulates sonic hedgehog pathway signaling through coordinated control of smoothened (SMO) ciliary trafficking with LTZL1. Loss-of-function TTC8 mutations cause two distinct disease phenotypes: Bardet-Biedl syndrome (BBS8), a multisystemic ciliopathy affecting kidney, retinal, reproductive, and olfactory systems 2, and nonsyndromic retinitis pigmentosa 51 (RP51), characterized by isolated retinal degeneration 3. Functionally, TTC8 represents a peripheral BBSome subunit with less critical roles in kidney development compared to core subunits, explaining variable clinical severity 1. The gene exhibits complex alternative isoform regulation in sensory tissues including the retina and pineal gland, with neural regulation of specific splice variants 4. Genome-wide association studies implicate the TTC8-containing chr14 locus in atherosclerotic phenotypes, suggesting broader vascular relevance 5. TTC8 mutations account for approximately 2.8% of BBS cases, establishing it as a minor but confirmed contributor to ciliopathic disease burden 6.