CRYL1 (crystallin lambda 1) is a metabolic enzyme that catalyzes the conversion of L-gulonate to 3-dehydro-L-gulonate using NAD as a cosubstrate, with additional low dehydrogenase activity toward L-3-hydroxybutyrate and L-threonate 1. The gene is located on chromosome 13.11 and shows highest expression in liver and kidney tissues 1. CRYL1 functions as a tumor suppressor in hepatocellular carcinoma (HCC), where reduced expression is associated with advanced tumor staging, increased tumor size, and shorter disease-free survival 2. Restoration of CRYL1 expression inhibits cellular proliferation and induces apoptosis through prolongation of the G2-M phase 2. The gene is frequently downregulated in liver cancer tissues through mechanisms including homozygous deletions, histone deacetylation, and promoter hypermethylation 2. CRYL1 variants have been associated with sickle cell disease nephropathy and may serve as a prognostic biomarker in clear cell renal cell carcinoma, correlating with immune infiltration and cuproptosis pathways 34. Additionally, CRYL1 deletions can affect GJB2 expression in cis, contributing to hearing loss phenotypes 56.