IQCN and Azoospermia: Furthermore, specific loss-of-function mutations disrupt sperm function through defined molecular pathways: IQUB mutations impair Ca2+/calmodulin-dependent regulation of flagellar radial spoke assembly, leading to asthenozoospermia (5, 14); IQCN mutations abolish protein translocation to the sperm equatorial segment, resulting in complete fertilization failure (16); and IQCH deficiency causes widespread splicing dysregulation, culminating in spermatogenic arrest and azoospermia (7).