CERKL (ceramide kinase-like) is a retinal protein that functions as a stress-response regulator despite lacking detectable ceramide kinase activity 1. CERKL localizes to multiple retinal compartments including mitochondria, the cytoplasm, and photoreceptor outer segments, with expression predominantly in cone photoreceptors and ganglion cells 2. The gene produces over 20 mRNA isoforms through multiple transcriptional start sites and alternative splicing, generating protein variants with distinct functional domains 3. Mechanistically, CERKL regulates retinal homeostasis through multiple pathways: it controls mitochondrial dynamics and autophagy 4, regulates photoreceptor outer segment phagocytosis by the retinal pigment epithelium via MERTK expression 5, and protects cells from oxidative stress-induced apoptosis 1. CERKL deficiency impairs glutathione metabolism and stress granule formation, creating a basal exacerbated stress state that compromises cellular responses to oxidative damage 1. CERKL mutations cause retinitis pigmentosa 26 and cone-rod dystrophy in humans, characterized by photoreceptor degeneration and progressive vision loss 5. In patient cohorts, CERKL variants were identified in 15.8% of Chinese families with retinitis pigmentosa exhibiting autosomal recessive inheritance 6. These findings establish CERKL as a critical resilience factor for maintaining retinal photoreceptor survival under physiological and stress conditions.