CHPF (chondroitin polymerizing factor) is a glycosyltransferase that plays a crucial role in chondroitin sulfate (CS) biosynthesis and has emerged as an important oncogene across multiple cancer types 1. The protein functions as part of heterodimeric complexes (CHSY1-CHPF, CHSY1-CHPF2, CHSY3-CHPF, and CHSY3-CHPF2) responsible for CS chain polymerization, where CHPF primarily serves a stabilizing role rather than direct enzymatic activity 2. CHPF is significantly upregulated in various malignancies including osteosarcoma, glioma, breast cancer, gastric cancer, and melanoma, where its overexpression correlates with poor prognosis and advanced tumor stages 34567. Mechanistically, CHPF promotes tumorigenesis through multiple pathways: activating AKT signaling and inhibiting SKP2 ubiquitination in osteosarcoma 3, interacting with MAD1L1 in glioma 4, stabilizing CS-syndecan-1 complexes to regulate macropinocytosis in breast cancer 5, activating E2F1 through UBE2T-mediated ubiquitination regulation in gastric cancer 6, and regulating CDK1 in melanoma 7. These findings establish CHPF as a promising therapeutic target for cancer treatment, with its multifaceted roles in cell proliferation, migration, and survival making it clinically significant across diverse malignancies.