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Acrosome plays an integral role during fertilization and its absence in individuals with globozoospermia leads to failure of in vitro fertilization (IVF) and oocyte activation post-intracytoplasmic sperm injection (ICSI). A variety of processes, organelles and structures are involved in acrosome biogenesis including, trans-golgi network (TGN), acroplaxome and cellular trafficking. This review aims to explain roles of related signals and molecules involved in this process and also describe how their absence in form of mutation, deletion and knockout model may lead to phe- nomenon referred to globozoospermia.