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Purpose: To investigate the expression of rhotekin 2 (RTKN2) in human endometrial carcinoma tissues and its role in cancer progression. Methods: Quantitative polymerase chain reaction (qPCR) and immunoblot assays were performed to determine the expression of RTKN2 in endometrial carcinoma tissues and cells. The effects of RTKN2 on cell proliferation were assessed using cell counting kit-8 and EdU assays, while its effects on cell cycle and apoptosis in endometrial carcinoma cells were evaluated by flow cytometry. The involvement of RTKN2 in activating Akt/glycogen synthase kinase-3 beta (GSK3β) pathway was characterized using an immunoblot assay. Tumor growth assays were performed to assess the effects of RTKN2 on the progression of endometrial carcinoma in vivo, while protein expression in tumor tissues was determined by an immunohistochemical assay. Results: High expression of RTKN2 was found in human endometrial carcinoma tissues and cell lines (p < 0.05). RTKN2 promoted the proliferation and cell cycle of endometrial carcinoma cells in vitro and suppressed apoptosis (p < 0.05). RTKN2 also activated Akt/GSK3β pathway in endometrial carcinoma cells and thus promoted tumor growth in vivo. Conclusion: The involvement of RTKN2 in the progression of endometrial carcinoma has been confirmed in this study. RTKN2 is thus a promising therapeutic target for patients with this disease.