LAUSR

Significance In mammals, multiple sperm acrosomal membrane proteins are indispensable for sperm–egg interaction, yet the mechanisms underlying their biosynthesis have remained unknown. This study reveals that mouse 1700029I15Rik stabilizes OST subunits important for N-glycosylation and specifically mediates the processing of acrosomal membrane proteins in the ER of early round spermatids. We propose that during spermiogenesis, the biosynthesis of proteins destined for different subcellular compartments is orchestrated in a spatiotemporal manner. Given that 1700029I15Rik is highly conserved in humans, our discoveries in mice may provide profound insights into the etiology of idiopathic male infertility and the development of a nonhormonal contraceptive approach involving molecular interventions in the biosynthesis of acrosomal membrane proteins.