RPL22L1 is a ribosomal protein component of the 60S ribosomal subunit with dual functions in translation and gene regulation 1. Beyond its structural role in cytoplasmic translation, RPL22L1 participates in alternative RNA splicing regulation; the RPL22L1b isoform promotes splicing through lncMALAT1 degradation in the nucleus, while RPL22L1a enhances translation of multiple mRNAs including TP53 in the cytoplasm 2. RPL22L1 is markedly upregulated across multiple cancer types including colorectal cancer, glioblastoma, prostate cancer, and cervical cancer, correlating with poorer prognosis 3415. Mechanistically, RPL22L1 promotes cancer progression through distinct pathways: EGFR/STAT3 signaling in glioblastoma where it confers temozolomide resistance 4, PI3K/Akt/mTOR pathway activation in prostate cancer 1, and DUSP6-ERK axis modulation in cervical cancer, promoting drug resistance 5. Additionally, RPL22L1 is regulated by ribosomal stress through RPL22-mediated alternative splicing 6. Beyond oncology, RPL22L1 serves as a shared diagnostic and prognostic biomarker in inflammatory arthropathies, associating with T cell infiltration and VEGF signaling 7. These findings establish RPL22L1 as a multifunctional oncogene and therapeutic target across malignancies.