Stomatin-like protein 2 (SLP-2) is a novel and unusual stomatin homologue of unknown functions. It was first identified to be overexpressed and involved in regulating cell growth and cell adhesion in human esophageal squamous cell carcinoma. We show herein the involvement of SLP-2 in human endometrial adenocarcinoma, and the effects of SLP-2 on endometrial adenocarcinoma cell growth. The expression of SLP-2 was evaluated in human endometrial adenocarcinoma by semi-quantitative RT-PCR, Westernblotting and immunohistochemistry. Sense and antisense SLP-2 eukaryotic expression plasmids were transfected into the human endometrial adenocarcinoma cell line HEC-1B. MTT assay and flow cytometry assay were performed to investigate the roles of the SLP-2 gene. SLP-2 was overexpressed in endometrial adenocarcinoma compared with their normal counterparts (P<or=0.05). Immunohistochemistry showed that SLP-2 was mainly localized in the cytoplasm with some distribution on the membrane. HEC-1B cells transfected with antisense SLP-2 showed decreased cell growth, whereas the cell growth increased with the sense transfection. SLP-2 was first identified as a novel cancer-related gene overexpressed in human endometrial adenocarcinoma. Cell growth changes with the sense and antisense transfection revealed that SLP-2 might be important in endometrial tumorigenesis.