SPACA1 (sperm acrosome associated 1) is a critical inner acrosomal membrane protein that plays an essential role in acrosome formation and establishment of normal sperm morphology during spermatogenesis 1. The protein localizes to the acrosomal equatorial segment and variable regions of the acrosomal principal segment 2. Mechanistically, SPACA1 functions as a component of the acrosome-acroplaxome complex, interacting with multiple proteins including ACTL7A, MFSD6L, HSP90B1, and cylicin-1 to anchor and stabilize acrosome structure 134. The protein is also involved in sperm capacitation and acrosome reaction pathways 5. Biallelic loss-of-function mutations in SPACA1 cause autosomal recessive globozoospermia, characterized by abnormally shaped sperm heads lacking proper acrosome structure 1. SPACA1 deficiency results in acrosome-acroplaxome complex damage and acrosomal hypoplasia 16. Clinically, SPACA1 distribution patterns correlate significantly with blastocyst development rates in conventional in vitro fertilization, suggesting potential use as a molecular biomarker for predicting fertility outcomes 2. While intracytoplasmic sperm injection can achieve pregnancy in SPACA1-deficient patients, natural conception is severely compromised due to acrosome dysfunction affecting sperm-egg interaction 1.