PGK2

PGK2 is a testis-specific phosphoglycerate kinase isozyme in the glycolytic pathway that provides ATP required for sperm motility^[1]. Its transcription activates in primary spermatocytes and supports normal mammalian sperm motility and fertility^[2]. Mechanistically, Pgk2 expression depends on stage-specific promoter and enhancer regulation, including PBX4, PREP1, CREM, and SP3 binding during spermatogenesis^[2]. Developmental studies show that PGK2 synthesis rises in spermatids, whereas PGK1 synthesis remains very low and relatively constant across spermatogenic stages^[3]. Compared with cytoplasmic PGK1, PGK2 has a nearly identical fold and active site but differs on the C-terminal domain surface, which may support sperm-flagellum protein interactions^[1]. In human sperm, PGK2 interacts with CABYR, linking this isoform to testis-specific calcium-binding protein networks^[4]. In disease-related models, seminal plasma PGK2 was lower in varicocele-associated asthenospermia and increased after varicocelectomy, supporting its use as a biomarker for sperm motility improvement^[5]. PGK2 and other spermatogenesis-associated retrogenes are also expressed in normal ovary and ovarian cancers, suggesting experimental relevance beyond male germ cells^[6].