{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n BBS9, originally identified as the parathyroid hormone–responsive gene B1, is emerging as a critical core component of the BBSome, a multimeric protein complex that regulates the trafficking of membrane proteins to and from primary cilia. Mutations in BBS9 have been linked to classic Bardet–Biedl syndrome (BBS) features—including retinal degeneration, obesity, polydactyly, and craniofacial abnormalities—and studies in diverse models have demonstrated that BBS9 is essential for proper ciliogenesis and ciliary signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " Structural studies have revealed that the N‐terminal domain of BBS9 adopts a seven‐bladed β–propeller fold that is well suited for mediating protein–protein interactions, an attribute that appears crucial for the proper assembly and stability of the BBSome."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Functional work in zebrafish and mammalian cell models further supports a conserved role for BBS9 in ciliary biogenesis, as its depletion results in shortened or fewer cilia and leads to developmental defects consistent with ciliopathies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, the dynamic regulation of BBS9 localization by proteins such as LZTFL1 suggests that its incorporation into the BBSome is tightly controlled to ensure proper ciliary function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Clinical and genetic studies implicate variants in BBS9 not only in the core features of Bardet–Biedl syndrome but also in traits related to skeletal development and adipose tissue distribution, underlining its pleiotropic impact on human development and metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Darryl Y Nishimura, Ruth E Swiderski, Charles C Searby, et al. 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