Abstract Introduction Infertility is defined as the incapability to achieve fertilization after 1 year following sexual intercourse without any contraceptive measure. Poor sperm quality contributes to 90% of male infertility. Spermatogenesis takes place in the seminiferous tubules of the testis by proliferation followed by complex morphologic, physiologic, and biochemical modifications that result in the formation of mature spermatozoa. These specific events are supported by spermiogenesis-specific gene products. During spermiogenesis, sperm chromatin undergoes a series of modifications in which histones are lost and replaced with transition proteins and subsequently with protamine. Replacement of histones to protamine is impotent in the formation of mature spermatozoa. Histones are important for DNA replication but in spermatogenesis histones replacement with protamine prevents DNA replication and causes sperm maturation. Any problem in this replacement may cause male infertility. The nuclei of elongated and condensing spermatids contain nuclear transition protein 1 (TNP1) and nuclear transition protein 2 (TNP2) but tnp2 is more effective. TNP2 plays a critical role in shaping sperm nucleus, displacement of histones with protamine condensation of chromatin, and binding of protamines to DNA. Objective This review aims to determine the association of a TNP2 polymorphism (G1272C) with the risk of male infertility. Methods PUBMED, CENTRAL, Google Scholar and PMC articles were searched, whereas case-control, published studies regarding TNP2 polymorphism (G1272C) and male infertility were selected for this meta-analysis. Results Based on literature search and inclusion criteria, 3 case-control studies out of the total 16 articles were selected, ranging from 2005 to 2019. The included case-control studies observing G1272C polymorphism in the TNP2 gene contained 534 cases and 516 controls. No significant association (p > 0.05) between G1272 polymorphism and male infertility was found, based on all of the three genetic models. Whereas, when we pooled the data of two population of same region i.e. Iran, significant association (p < 0.05) was found between G1272C polymorphism and male infertility on the basis of additive model (CC vs GG: OR= 0.34, 95% CI [0.20-0.56], I2 = 81%), dominant model (CC+CG vs GG: OR= 0.46, 95% CI [0.32-6.67], I2 = 91%) & recessive model (CC vs CG + GG: OR= 0.48, 95% CI [0.31-0.76], I2 = 85%), showing that this polymorphism might contribute to the male infertility, depending upon the ethnicity. Conclusions TNP2 G1272C may play role in male infertility suggested by the significant association in the Iranian population. Disclosure No