Iqub, encoding the IQUB protein, is highly and specifically expressed in murine testes. It is involved in regulating the assembly of sperm radial spoke, a key structure in sperm flagella that modulates the beat frequency, amplitude, and waveform of flagella and cilia. IQUB may recruit calmodulin in lower Ca2+ environments to facilitate the normal assembly of radial spokes by inhibiting the activity of RSPH3/p-ERK1/2, and is thus crucial for sperm motility [1].

Iqub knockout (KO) and knockin (KI) mouse models have been constructed to study its function. Both KO and KI mice mimic the infertility phenotype observed in affected humans, with sperm showing radial spoke defects. This indicates that IQUB is a pathogenetic gene for male infertility characterized by asthenospermia [1]. In another mouse model, deletion of Iqub led to the lack of the entire RS1 in sperm flagella, while tracheal cilia had intact triple RSs, resulting in male infertility due to sperm motility defect, further elucidating the role of IQUB in regulating mammalian RS1 assembly and sperm flagellar beat [2,3].

In conclusion, Iqub plays an essential role in the assembly of sperm radial spoke and sperm motility. Studies using Iqub KO and KI mouse models have revealed its crucial role in male infertility caused by asthenospermia, expanding our understanding of the genetic factors involved in this condition.