{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CC2D2A is a key component of the ciliary transition zone that regulates both the assembly of primary cilia and the trafficking of membrane‐associated proteins. It localizes at the basal body and subdistal appendages where it helps to establish a selective diffusion barrier, thereby controlling the composition of the ciliary membrane and ensuring proper signaling through pathways such as Hedgehog. Genetic studies have shown that loss‐of‐function or hypomorphic mutations in CC2D2A disrupt cilia formation and protein localization, leading to a spectrum of ciliopathies; milder (hypomorphic) alleles are associated with Joubert syndrome, whereas null alleles are linked to the more severe, often lethal, Meckel–Gruber syndrome (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " Furthermore, detailed genotype–phenotype correlations indicate that the degree of disruption in CC2D2A function directly influences clinical outcome, as reinforced by studies showing that more deleterious mutations lead to more severe phenotypes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": " Animal and cellular models further confirm that loss of CC2D2A causes defective ciliogenesis, impaired ciliary protein trafficking, and altered organogenesis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Notably, recent ex vivo investigations reveal tissue‐specific basal exon skipping within CC2D2A transcripts that may, in the future, be amenable to therapeutic exon‐skipping approaches."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Collectively, these findings underscore the pivotal role of CC2D2A in maintaining correct ciliary architecture and function, with its disruption underpinning multiple ciliopathy phenotypes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Francesc R Garcia-Gonzalo, Kevin C Corbit, María Salomé Sirerol-Piquer, et al. 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