COL4A6 encodes the alpha-6 chain of type IV collagen, a major structural component of basement membranes that forms a 'chicken-wire' meshwork with laminins and proteoglycans 1. The protein is part of the α5α5α6(IV) collagen heterotrimer and is expressed in a tissue-specific manner from two alternative promoters, with transcripts from exon 1' predominating in placenta and exon 1 transcripts more abundant in kidney and lung 2. COL4A6 is located head-to-head with COL4A5 on chromosome X, spanning approximately 425 kb with 46 exons 3. COL4A6 mutations cause X-linked deafness-6 through disruption of basement membrane integrity in the inner ear 4. Notably, contiguous deletions affecting both COL4A6 and COL4A5 cause Alport syndrome-diffuse leiomyomatosis, a rare variant characterized by renal failure and smooth muscle overgrowth in visceral organs; inactivation of both genes is required for the leiomyomatosis phenotype 5. COL4A6 mutations also contribute to Alport syndrome when inherited with COL4A3/COL4A4 variants in digenic inheritance patterns 6. In prostate cancer, COL4A6 downregulation via promoter hypermethylation activates p-FAK/MMP-9 signaling, promoting invasion and metastasis, and COL4A6 expression correlates with improved disease-free survival 7.