EXTL1 (exostosin like glycosyltransferase 1) is a glycosyltransferase required for heparan sulfate (HS) biosynthesis. The protein catalyzes N-acetyl-alpha-D-glucosamine transfer to nascent HS chains via GlcNAcT-II activity, functioning primarily in chain elongation rather than initiation 1. Unlike some EXT family members, EXTL1 lacks GlcNAcT-I and GlcAT-II activities 1. Mechanistically, EXTL1 promotes heparan sulfate proteoglycan (HSPG) production through its glycosyltransferase domain. Recent evidence demonstrates that EXTL1-mediated HSPG synthesis inhibits C1q expression, thereby enhancing CCR7 surface expression on dendritic cells and promoting their migration to draining lymph nodes 2. This function is critical for initiating protective immune responses against bacterial infection and maintaining immune tolerance through Treg cell development 2. EXTL1 maps to chromosome 1.1, a region frequently deleted in various malignancies including neuroblastoma 34. The gene spans 11 exons within a 50-kb genomic region 3. However, mutation screening in neuroblastoma patients found limited evidence supporting EXTL1 as a primary tumor suppressor 4. Notably, EXTL1 expression is downregulated during ferroptosis-induced immune remodeling in pancreatic cancer, correlating with altered glycosylation patterns and enhanced antitumor immunity 5.