This study integrated transcriptomic analysis with multidimensional bioinformatics approaches to systematically elucidate the regulatory roles of AAA+ ATPase family members in clear cell renal cell carcinoma (ccRCC). Through differential expression analysis of TCGA and GEO databases and construction of weighted gene co-expression networks (WGCNA), the key gene TRIP13 was identified. Experimental validation revealed that TRIP13 is significantly upregulated in ccRCC tissues and closely associated with poor patient prognosis, with high expression correlating with markedly reduced overall survival and progression-free survival. Molecular mechanism studies demonstrated that TRIP13 promotes tumor proliferation and migration by activating cell cycle-related pathways (e.g., G2/M checkpoint, E2F targets, normalized enrichment score?>?3.0, p?<?0.01). Single-cell RNA sequencing further revealed its specific enrichment during the S/G2M phase and regulation of proliferation marker genes such as PCNA. Inhibitor interaction analysis confirmed that DCZ0415 and TI17 synergistically suppress TRIP13 function by targeting critical residues like SER-187. Additionally, TRIP13 expression was positively correlated with the infiltration of effector memory T cells in the tumor microenvironment, suggesting its potential role in immunoregulation. This study identifies TRIP13 as a novel therapeutic target and prognostic biomarker for ccRCC, offering insights into targeted therapy and personalized treatment strategies.