B9D2 is a ciliary transition zone protein that functions as a critical component of the B9 protein complex (MKS1-B9D2-B9D1) 1. As part of the tectonic-like complex at the ciliary base, B9D2 acts as a gatekeeper to prevent diffusion of transmembrane proteins between cilia and plasma membranes 1. Beyond its barrier function, B9D2 regulates ciliary axonemal microtubule posttranslational modifications through interaction with TMEM67 and facilitates ciliogenesis initiation at centrioles 2. Additionally, B9D2 maintains tight junction integrity and epithelial polarity prior to ciliogenesis, supporting biliary lumen formation 3. B9D2 mutations cause ciliopathies with distinct phenotypes depending on variant type. Joubert syndrome-associated variants primarily impair axonemal microtubule modifications while preserving ciliogenesis 24, whereas Meckel syndrome variants disrupt both ciliogenesis and microtubule modifications 25. B9D2 mutations account for disease in both syndromes 65. Preliminary evidence suggests B9D2 may serve as a non-invasive peripheral blood biomarker for colorectal cancer detection, though clinical validation is needed 7.