CCDC158 is a coiled-coil domain protein that plays a critical role in receptor-mediated endocytosis in renal proximal tubular cells 1. The protein functions as a regulator of clathrin-coated vesicle trafficking and early endosomal processing, likely through interactions with other endocytosis-related proteins 1. Functional studies using transferrin and GST-RAP trafficking assays in patient-derived proximal tubular epithelial cells confirmed CCDC158's role in receptor-mediated endocytosis 1. Genetically, loss of heterozygosity (LOH) at the CCDC158 locus on chromosome 4.1 is associated with larger tumor size in hepatocellular carcinoma patients 2. Additionally, genetic variants in CCDC158 are part of a chromosome 4.1 locus associated with kidney function markers, though SHROOM3 appears to be the primary effector gene 3. Biallelic CCDC158 mutations cause a clinical phenotype of low- and intermediate molecular weight proteinuria, nephrocalcinosis, and oligospermia, highlighting its importance in both renal tubular reabsorption and male fertility 1. These findings establish CCDC158 as a novel regulator of proximal tubular endocytic pathways with potential implications for kidney disease and cancer biology.