Col4a4, encoding the α4 chain of type IV collagen, is a crucial gene. Type IV collagen is the major component of the glomerular basement membrane (GBM), playing an essential role in maintaining the structure and function of the GBM [1,2,3,5,6,7,9]. Mutations in Col4a4 can disrupt the normal assembly and function of type IV collagen in the GBM, which is associated with multiple kidney - related diseases [1,2,3,4,5,6,7,8,9].

Mutations in Col4a4 are linked to autosomal recessive and autosomal dominant Alport syndrome [2,3]. In autosomal recessive Alport syndrome, two pathogenic mutations in Col4a4 can lead to progressive renal failure, hearing loss, and ocular abnormalities, with the median age at end - stage renal failure being 22.5 years in affected individuals [2]. For autosomal dominant Alport syndrome associated with heterozygous pathogenic Col4a4 variants, the risk of end - stage kidney failure is relatively low, occurring in fewer than 3% of those with pathogenic variants by the age of 60 [3]. Also, in sporadic IgA nephropathy patients with thinned glomerular basement membrane lesions, diagnostic variants of Col4a4 were identified, and patients with these variants had specific features such as higher proportions of GBM thickness <250 nm and milder glomerular injury [1].

In conclusion, Col4a4 is vital for the normal structure and function of the glomerular basement membrane. Studies on Col4a4 - related mutations in models like those with Alport syndrome and IgA nephropathy have significantly enhanced our understanding of the role of Col4a4 in kidney - related diseases, providing insights into disease mechanisms and potential diagnostic and therapeutic strategies.