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Endoplasmic reticulum stress (ERS) is associated with breast cancer progression. However, the potential role of ribosomal protein L5 (RPL5) on ERS in breast cancer remains unclear. This study aimed to determine the role of RPL5/E2F transcription factor 1 (E2F1) in breast cancer. It was found that RPL5 was downregulated in breast cancer cells and tissues. Additionally, overexpression of RPL5 inhibited cell proliferation. Moreover, the levels of ERS and autophagy markers were estimated using western blotting. Overexpression of RPL5 induced ER