Ift81, a core component of the IFT-B complex, is crucial for intraflagellar transport (IFT), which is essential for the construction and maintenance of cilia and flagella. Cilia are vital cellular organelles for signaling and motility, and IFT mediates intraciliary bidirectional trafficking as well as the import and export of ciliary proteins [1,2,4,5,6,7,8]. Ift81 has been associated with multiple biological processes and disease conditions related to ciliopathies [1,2,3,4,5].

In male mice, disruption of Ift81 expression starting from the spermatocyte stage led to complete infertility. Spermatozoa showed dysmorphic and nonfunctional flagella, along with abnormal spermiogenesis. The expression levels of several IFT components in testes were significantly reduced in homozygous mutant mice, indicating Ift81's essential role in spermatogenesis by modulating sperm flagella assembly and elongation [6]. In human cells, knockdown of Ift81 and rescue experiments with point mutants demonstrated that tubulin binding by Ift81 was required for ciliogenesis. Together, Ift81 and Ift74 N-termini likely function as the main module for IFT of tubulin, as shown by studies in Chlamydomonas mutants [7,8]. Also, compound heterozygous variations of Ift81 in a skeletal ciliopathy patient caused defects in its interactions with other IFT-B subunits, ciliogenesis, and ciliary protein trafficking [1].

In conclusion, Ift81 is essential for cilia-related functions such as ciliogenesis, sperm flagella formation, and ciliary protein trafficking. Gene knockout models in mice and other genetic models have been instrumental in revealing its role in male infertility and skeletal ciliopathies, among others. Understanding Ift81's functions provides insights into the mechanisms of ciliopathies and potential therapeutic targets.