Recent studies have found that cytoskeleton-associated protein 2 like (), an important oncogene, is involved in the biological behavior of many malignant tumors, but its function in the malignant course of glioma has not been confirmed. The main purpose of this study was to clarify the relationship between prognostic clinical characteristics of glioma patients and expression using data collected from the GEPIA, HPA, CGGA, TCGA, and GEO databases. expression was significantly increased in glioma. Further, Kaplan-Meier plots revealed that increased expression of was associated with shorter survival time of glioma patients in datasets retrieved from multiple databases. Cox regression analysis indicated that can serve as an independent risk factor but also has relatively reliable diagnostic value for the prognosis of glioma patients. The results of gene set enrichment analysis suggested that may play a regulatory role through the cell cycle, homologous recombination, and N-glycan biosynthesis cell signaling pathways. Several drugs with potential inhibitory effects on were identified in the CMap database that may have therapeutic effects on glioma. Finally, knockdown of CKAP2L inhibited the proliferation and invasion of cells by reducing the expression level of cell cycle-related proteins. This is the first study to demonstrate that high CKAP2L expression leads to poor prognosis in glioma patients, providing a novel target for diagnosis and treatment of glioma.