DGKK encodes diacylglycerol kinase κ, an enzyme that converts diacylglycerol (DAG) into phosphatidic acid (PA), thereby regulating levels of these two bioactive lipids and acting as a molecular switch between signaling pathways with opposing cellular effects. The gene is expressed in preputial tissue and responds to oxidative stress through changes in intracellular signaling and mitochondrial respiration. DGKK variants are strongly associated with hypospadias susceptibility in multiple populations, though with notable phenotypic heterogeneity. In European and Han Chinese populations, common single nucleotide polymorphisms (SNPs) show robust association with mild and moderate hypospadias 1234, with allele-specific odds ratios ranging from 1.6 to 3.9. Expression studies demonstrate that carriers of the hypospadias risk allele rs1934179 exhibit lower DGKK expression in preputial tissue 1. However, severe hypospadias appears genetically heterogeneous, with most studies showing no significant DGKK association in severe cases 25, suggesting distinct etiologic pathways by phenotypic severity. Beyond hypospadias, DGKK duplications on chromosome X.22 associate with syndromic intellectual disability, speech delay, and precocious puberty 6. Recent evidence suggests DGKK activation may contribute to hepatoma cell death in response to pharmacologic ascorbate through oxidative stress pathways 7. Additionally, DGKK mutations have been identified as candidate pathogenic variants in severe aplastic anemia 8, though the mechanism requires further investigation.