Cilia- and flagella-associated protein 45 (CFAP45)

Cilia- and flagella-associated protein 45 (CFAP45) is an AMP-binding protein localized to the axoneme of motile cilia and flagella, where it plays a crucial role in the regulation of ciliary and flagellar beating through maintenance of adenine nucleotide homeostasis and facilitation of dynein ATPase activity[1][4]. It interacts with axonemal proteins including dynein ATPases, adenylate kinase AK8, and CFAP52, and its loss leads to disorders of ciliary movement manifesting as situs abnormalities (such as situs inversus totalis) and male infertility (asthenospermia) due to defective sperm motility[1][2]. CFAP45 has been identified in human respiratory cilia and sperm and is evolutionarily conserved in ciliated organisms[1][2]. It is linked to the establishment of left-right body asymmetry and proper function of motile cilia in tissues such as the respiratory epithelium and male reproductive tract[3][4]. CFAP45 deficiency in humans and mice causes subtle defects in microtubule sliding and results in clinical features of primary ciliary dyskinesia without apparent structural defects in axonemal ultrastructure[1][2]. Key points: - Not classified as a classical drug target (e.g., receptor, enzyme, transporter), but as a structural and regulatory component of the ciliary axoneme. - No known small molecule drugs or therapeutic ligands reported to interact directly with CFAP45. - Loss-of-function mutations cause human disease but there are no approved therapies directly targeting CFAP45. - Mechanistically, it supports ciliary motility by maintaining adenine nucleotide homeostasis in cooperation with dynein ATPases and AK8[1][2][4].

Other names

CCDC19NESG1Coiled-coil domain-containing protein 19Nasopharyngeal epithelium-specific protein 1HTX11protein CFAP45, mitochondrialnasopharyngeal epithelium specific protein 1