BBS5 is a core component of the BBSome complex, which functions as a coat complex essential for sorting and trafficking of membrane proteins to the primary cilium 1. BBS5 localizes to basal bodies and is necessary for ciliogenesis in both motile flagella and primary cilia 1. The BBSome mediates ciliary protein transport by associating with RAB3IP/Rabin8, a guanine nucleotide exchange factor for Rab8, which promotes docking and fusion of carrier vesicles at the ciliary base. BBS5 also regulates sonic hedgehog signaling through control of SMO ciliary trafficking. BBS5 mutations cause Bardet-Biedl syndrome (BBS), a ciliopathy presenting with obesity, polydactyly, hypogonadism, intellectual disability, and retinal degeneration 2. Bbs5-knockout mice recapitulate human disease with hyperphagia, metabolic dysfunction, pituitary abnormalities, and impaired insulin, leptin, and cholecystokinin signaling 3. Notably, developmental Bbs5 loss causes fertility defects and ventriculomegaly, while postnatal mutation independently drives obesity 2. A retina-specific BBS5 splice variant exists with restricted expression in photoreceptor connecting cilia 4. BBS5 expression is transcriptionally regulated by PITX2 in trabecular meshwork cells, potentially linking BBS5 to glaucoma pathology 5. Clinically, GLP-1 receptor agonists show therapeutic promise for managing BBS-associated metabolic dysregulation 3.