LRRC37A is an acrosomal protein required for acrosome integrity and sperm head morphogenesis

Fertilization depends on the proper formation and function of the acrosome, a specialized organelle essential for sperm-oocyte interaction. Defects in acrosome biogenesis impair fertilization and cause severe male infertility, including globozoospermia. However, the molecular mechanisms underlying acrosome formation and maintenance remain poorly understood. Here, we investigated the roles of the testis-enriched proteins LRRC37 and LRRC37A using knockout (KO) mouse models. While Lrrc37 KO males were fertile with only mild sperm head abnormalities, Lrrc37a KO males were completely infertile and produced round-headed spermatozoa characteristic of globozoospermia. LRRC37A localized to the acrosome, and its loss resulted in abnormal acrosome enlargement accompanied by the accumulation of Golgi- and vesicle-like structures. Acrosome formation in Lrrc37a KO mice appeared normal during early spermiogenesis but became abnormal at later stages, indicating a requirement for LRRC37A in acrosomal structural integrity. These defects were associated with impaired sperm head shaping during spermiogenesis, leading to globozoospermia. Together, these findings establish LRRC37A as an essential factor in maintaining acrosome integrity and sperm head morphogenesis, highlighting its distinct function from LRRC37. This work provides new insight into the molecular basis of acrosome-related infertility and has important implications for understanding the etiology of globozoospermia.