Inherited retinal diseases (IRDs) encompass a genetically diverse group of conditions in which mutations in genes critical to retinal function lead to progressive loss of photoreceptor cells and subsequent visual impairment. A handful of ribosome-associated genes have been implicated in retinal disorders alongside neurological phenotypes. This study focuses on the HBS1L gene, encoding HBS1 Like Translational GTPase which has been recognized as a critical ribosomal rescue factor. Previously, we have reported a female child carrying biallelic HBS1L mutations, manifesting growth restriction, developmental delay, and hypotonia. In this study, we describe the ophthalmologic findings using the Hbs1ltm1a/tm1a hypomorph mouse model and evaluate the underlying microscopic and molecular perturbations. Hbs1ltm1a/tm1a mice exhibited profound retinal thinning of the entire retina, specifically of the outer retinal photoreceptor layer, detected using in vivo imaging of optical coherence tomography (OCT) and retinal cross sections. TUNEL assay revealed retinal degeneration due to extensive photoreceptor cell apoptosis. Loss of HBS1L resulted in comprehensive proteomic alterations in mass spectrometry analysis, with169 proteins upregulated and 480 proteins downregulated. GO biological process and GSEA analyses reveal that these downregulated proteins are primarily involved in photoreceptor cell development, cilium assembly, phototransduction, and aerobic respiration.