Immune microenvironment analysis showed that TMEM72 was predominantly expressed in epithelial and malignant cells and was positively associated with infiltration of anti-tumor immune cells, including M1 macrophages, monocytes, and NK cells, but negatively correlated with immunosuppressive populations such as regulatory T cells and M0 macrophages.<h4>Conclusions</h4>TMEM72 suppresses RCC progression by promoting p38/MAPK-dependent cellular senescence and may contribute to tumor immune microenvironment remodeling, highlighting its potential as a prognostic biomarker and therapeutic target. Here, TMEM72 is linked to renal cell carcinoma.