Lrrc23, a leucine-rich repeat-containing protein, is an essential component of the radial spoke (RS) complex, especially in the head assembly of RS3. RSs are T-shaped multiprotein complexes on axonemal microtubules that couple the central pair to modulate ciliary and flagellar motility [1,2]. Lrrc23 is crucial for sperm motility and male fertility, and may also be involved in other biological processes such as embryonic palate osteogenesis [4].

In infertile male patients with defective sperm motility, variants of Lrrc23 have been identified. Mouse models mimicking these variants produce truncated Lrrc23 at the C-terminus, which fails to localize to the sperm tail, leading to male infertility due to defective sperm motility. The knockout of Lrrc23 in mice results in male infertility because of RS disorganization and impaired sperm motility, while ciliary beating is not significantly affected [1,2,3]. In zebrafish, mutations in lrrc23 lead to otolith formation defects during early ear development, specifically affecting ciliary motility in the otic vesicle [5].

In conclusion, Lrrc23 is a key regulator for the integrity of the RS complex within the flagella of mammalian spermatozoa, being essential for sperm motility and male fertility. Studies using knockout mouse models and zebrafish mutants have revealed its important role in male infertility and otolith development, providing insights into the molecular mechanisms underlying these biological processes and diseases [1,2,3,5].