Alternative splicing (AS) is a process in which precursor messenger RNA (pre-mRNA) splicing sites are differentially selected to diversify the protein isoform population. Changes in AS patterns have an essential role in normal development, differentiation and response to physiological stimuli. It is documented that AS can generate both “risk” and “protective” splice variants that can contribute to the pathogenesis of several diseases including atherosclerosis. The main endothelial receptor for oxidized low-density lipoprotein (ox-LDLs) is LOX-1 receptor protein encoded by the OLR1 gene. When OLR1 undergoes AS events, it generates three variants: OLR1, OLR1D4 and LOXIN. The latter lacks exon 5 and two-thirds of the functional domain. Literature data demonstrate a protective role of LOXIN in pathologies correlated with LOX-1 overexpression such as atherosclerosis and tumors. In this review, we summarize recent developments in understanding of OLR1 AS while also highlighting data warranting further investigation of this process as a novel therapeutic target.

Background: INPP5E-related retinopathy (INPP5E-RR) is a rare genetic disorder caused by biallelic pathogenic variants in the INPP5E gene, which encodes an enzyme critical for phosphoinositide signaling. While early-onset rod–cone dystrophy is a hallmark feature, detailed longitudinal data on the phenotype are scarce. This study aims to report a 6-year longitudinal assessment of retinal structure and function in a case of non-syndromic INPP5E-RR. Methods: A 42-year-old female proband with compound heterozygous pathogenic missense variants in INPP5E (p.Arg486Cys and p.Arg378Cys) was monitored from 2019 to 2025. She underwent serial comprehensive ophthalmologic evaluations, including optical coherence tomography (OCT), fundus autofluorescence, adaptive optics transscleral flood illumination, full-field 30Hz flicker electroretinography (ERG), and macular frequency-doubling technology perimetry. Results: Over the 6-year follow-up, OCT imaging revealed a progressive decline in the ellipsoid zone (EZ) width, from 1220 µm to 720 µm (~80 µm/year), and in the inner nuclear layer (INL) thickness. The central outer nuclear layer (ONL) thickness was preserved, but intraretinal cysts developed. Functional testing revealed a progressive decline in cone flicker ERG amplitudes, while visual acuity and macular perimetry remained stable. Conclusions: In this genotypically confirmed case, the longitudinal data identify EZ width, INL thickness, and cone flicker ERG as robust biomarkers of disease progression in INPP5E-RR. These parameters are ideal candidates for monitoring therapeutic outcomes in future clinical trials.