Background: Retinoblastoma (RB) is a highly aggressive pediatric ocular malignancy whose molecular mechanisms remain unclear. Although implicated in various cancers, the amino acid transporter Solute Carrier Family 38 Member 5 (SLC38A5) remains uncharacterized in RB. Herein, we aimed to investigate the expression pattern, biological functions, and underlying mechanisms of SLC38A5 in RB.

Methods: SLC38A5 expression was analyzed in human RB cell lines using Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). Functional characterization was performed through genetic manipulation (knockdown/overexpression) followed by comprehensive phenotypic assessment. In vivo xenograft models were used to evaluate tumor growth.

Results: SLC38A5 was significantly overexpressed in RB cell lines, particularly in Y79 and WERI-Rb1 (p < 0.001). SLC38A5 knockdown suppressed cell proliferation, migration, and invasion, and induced apoptosis (p < 0.05). Conversely, SLC38A5 overexpression enhanced these malignant phenotypes (p < 0.05). Additionally, SLC38A5 modulated mitochondrial function via the mTOR signaling pathway (p < 0.05). In vivo, SLC38A5 overexpression promoted tumor growth, whereas knockdown inhibited tumor progression (p < 0.05).

Conclusion: SLC38A5 acts as a key regulator of RB progression by modulating core biological processes, including proliferation, migration, invasion, and mitochondrial function. Targeting SLC38A5 may represent a potential therapeutic strategy for RB.