{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CFAP44 is a cilia‐ and flagella‐associated protein that plays an essential role in the proper assembly and function of motile flagella. In human spermatozoa, CFAP44 is highly expressed in the testis, and biallelic loss‐of‐function mutations in this gene have been shown to cause multiple morphological abnormalities of the sperm flagella (MMAF), leading to impaired sperm motility and male infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n Animal models generated via CRISPR/Cas9 confirm that disruption of CFAP44 leads to defects in flagellar morphogenesis and motility, underscoring its conserved function across species.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the ultrastructural and molecular levels, CFAP44 is an integral part of a protein complex that interacts with the inner dynein arm f. Studies using cryoelectron tomography and biochemical analyses have demonstrated that CFAP44, together with other WD‐repeat proteins, forms a tether complex that anchors the dynein motor domains to the A-tubule of the axoneme. This tethering limits nucleotide-dependent conformational motions of dynein, thus ensuring a controlled and coordinated flagellar beat."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Furthermore, altered expression of CFAP44 has been observed under environmental stress conditions. For example, exposure to fluoride leads to down-regulation of CFAP44 (alongside other flagellum-associated genes), resulting in disruption of the axonemal structure and a consequent reduction in sperm motility."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, reduced levels of CFAP44 and its associated long noncoding RNA have been correlated with abnormal sperm morphology and motility in infertile men with asthenozoospermia and terato-asthenozoospermia."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CFAP44 is critical for the proper organization and function of the sperm flagellum. By contributing to the assembly of axonemal structures and ensuring coordinated dynein activity, CFAP44 enables effective flagellar beating. Disruption of its function—whether by genetic mutation or environmental factors—leads to structural defects and impaired motility, ultimately contributing to male infertility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Shuyan Tang, Xiong Wang, Weiyu Li, et al. 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