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The B9D1-B9D2-MKS1protein complex maintains the gatekeeper function at the ciliary transition zone (TZ). However, the function of B9 proteins and the mechanisms underlying why different variants in the same B9 gene cause different ciliopathies are not fully understood. Here, we investigated the function of B9 proteins and revealed 2 critical functions. First, the B9 complex interacted with and anchored TMEM67 to the TZ membrane. Disruption of the B9-TMEM67 complex reduced posttranslational modifications of axonemal microtubules due to deregulation of tubulin-modifying enzymes within cilia. Second, B9 proteins localized to centrioles prior to ciliogenesis, where they facilitated the initiation of ciliogenesis. In addition, we identified\n                    <jats:italic>B9D2<\/jats:italic>\n                    variants in a cohort of patients with Joubert syndrome. We found that Joubert syndrome\u2013associated\n                    <jats:italic>B9D2<\/jats:italic>\n                    variants primarily affected axonemal microtubule modifications without disrupting ciliogenesis, whereas the Meckel syndrome\u2013associated\n                    <jats:italic>B9D2<\/jats:italic>\n                    variant disrupted both ciliogenesis and axonemal microtubule modifications. Thus, besides its role as a gatekeeper for ciliary membrane proteins, the B9 complex also controls axonemal microtubule posttranslational modifications and early stages of ciliogenesis, providing insights into the distinct pathologies arising from different variants of the same gene.\n                  <\/jats:p>","DOI":"10.1172\/jci196365","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T16:00:27Z","timestamp":1761840027000},"source":"Crossref","is-referenced-by-count":0,"title":["Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis"],"prefix":"10.1172","volume":"136","author":[{"given":"Ruida","family":"He","sequence":"first","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of 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