DCST1 (DC-STAMP domain containing 1) is a sperm cell-surface protein with dual roles in fertilization and potentially in disease regulation. Primary function: DCST1 is an essential factor for mammalian gamete fusion, mediating sperm-egg recognition and fusion through a phagocytosis-like mechanism termed SEAL (sperm engulfment activated by IZUMO1-JUNO linkage) 1. Working alongside sperm partners DCST2, SPACA6, TMEM95, FIMP, and FIMP, DCST1 facilitates the engulfment of spermatozoa by oocyte microvilli during fertilization 12. Mechanism: The protein functions as an E3 ubiquitin-protein ligase catalyzing Lys-48-linked ubiquitination of STAT2, leading to proteasomal degradation and negative regulation of type-I interferon signaling. Disease relevance: While DCST1 protein's direct involvement in disease remains undocumented in provided abstracts, the DCST1-AS1 long noncoding RNA (transcribed from the DCST1 locus) is significantly dysregulated in multiple cancers. DCST1-AS1 upregulation promotes malignant progression in pediatric acute myeloid leukemia, colorectal cancer, glioblastoma, and hepatocellular carcinoma through distinct epigenetic and post-transcriptional mechanisms 3456. Clinical significance: DCST1-AS1 represents a prognostic biomarker and potential therapeutic target in multiple cancer types, though the protein DCST1's clinical relevance beyond fertilization requires further investigation.