Ift81 is a core component of the IFT-B complex, which is involved in the bidirectional transport of ciliary proteins through intraflagellar transport (IFT) [2,3,4,6]. IFT is essential for the formation and maintenance of cilia and flagella, and thus, Ift81 is crucial for many biological processes relying on these organelles, such as cell signaling and motility [1,7]. Cilia-related functions are integral to numerous pathways, and defects in Ift81 can lead to ciliopathies [2,3,5,6].

In male mice, disruption of Ift81 expression starting from the spermatocyte stage led to complete infertility, abnormal sperm parameters, and abnormal spermiogenesis. Spermatozoa had dysmorphic and non-functional flagella, and there was a disorganization of axoneme and para-axonemal structures. The expression levels of several other IFT components in testes were also significantly reduced [7]. In Ift81-knockout (KO) cells, expression of certain Ift81 variants caused defects in its interactions with other IFT-B subunits, ciliogenesis, and ciliary protein trafficking, mimicking Bardet-Biedl syndrome-like ciliary defects [2]. In zebrafish, compound heterozygous mutations in Ift81 affected ciliogenesis, with a missense variant showing reduced rescue efficiency in Ift81-knockdown systems [4].

In conclusion, Ift81 is vital for the assembly and function of cilia and flagella, playing a key role in processes like spermatogenesis. Research using KO mouse models and other genetic models has revealed its significance in ciliopathies, including Bardet-Biedl syndrome-like disorders, and in nonsyndromic retinal degeneration, highlighting its importance in understanding cilia-related disease mechanisms [2,4,7].