CFAP77 is a microtubule inner protein (MIP) localized to the axoneme of motile cilia and sperm flagella, where it functions as a structural component of dynein-decorated doublet microtubules 1. The protein is essential for maintaining axonemal integrity and enabling proper flagellar function, as CFAP77 knockout mice exhibit significantly reduced sperm motility and male fertility despite normal sperm morphology 1. Mechanistically, CFAP77 stabilizes other MIPs through direct protein-protein interactions; specifically, it interacts with TEKTL1, and CFAP77 loss reduces TEKTL1 abundance in spermatozoa 1. Beyond reproductive function, CFAP77 has emerged as a potential biomarker in neurological disease contexts. Genome-wide association studies identified differentially methylated CpG sites in CFAP77 associated with opioid dependence in women 2, and SNPs within the CFAP77 gene region showed significant association with longitudinal changes in cerebrospinal fluid tau, a key Alzheimer's disease biomarker 3. These findings suggest CFAP77 may have broader biological significance beyond ciliary/flagellar function, though the mechanistic basis for its involvement in neurological phenotypes requires further investigation.