PGK2 (phosphoglycerate kinase 2) is a testis-specific glycolytic enzyme that catalyzes the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate 1. Unlike the ubiquitous somatic PGK1, PGK2 is an intronless processed gene expressed exclusively in late spermatogenesis 1, likely as a compensatory mechanism when PGK1 is silenced in male germ cells 1. PGK2 expression is tightly regulated through tissue-specific transcriptional mechanisms involving testis-specific factors (PBX4, PREP1, CREM, SP3) binding to promoter and enhancer elements 2, accompanied by DNA demethylation and chr6 remodeling during primary spermatocyte development 3. PGK2 is essential for normal sperm motility and male fertility 2, with lactylation at multiple lysine residues (particularly K220) modulating its enzymatic activity and glycolytic flux 4. In asthenozoospermia, reduced PGK2 lactylation correlates with decreased enzyme activity and impaired sperm motility 4. Clinically, seminal PGK2 protein levels and testicular PGK2 expression serve as predictive biomarkers for sperm retrieval success in non-obstructive azoospermia patients undergoing micro-TESE 56, with expression also correlating with retrieved sperm quality 6.