COL4A5 encodes the α5 chain of type IV collagen, a critical structural component of glomerular basement membranes (GBM) that assembles with α3 and α4 chains to form collagen IV α3α4α5 heterotrimers 1. This collagen forms a 'chicken-wire' meshwork providing tensile strength and structural integrity to basement membranes across multiple tissues. Mutations in COL4A5 cause X-linked Alport syndrome, the most common form of the disease, characterized by progressive kidney disease, sensorineural hearing loss, and ocular abnormalities 2. COL4A5 mutations account for approximately 80-85% of Alport syndrome cases and show variable severity depending on mutation type: protein-truncating variants prevent α3α4α5(IV) synthesis and cause earlier renal failure, while missense variants allow some heterotrimers to form but cause endoplasmic reticulum stress and impaired collagen trafficking 13. Disease mechanisms involve activation of endothelin-A receptors and collagen receptors (integrins and discoidin domain receptor 1) leading to progressive glomerulosclerosis 1. COL4A5 variants also contribute to sporadic IgA nephropathy with thinned GBM lesions and focal segmental glomerulosclerosis 4. Early genetic diagnosis is clinically crucial as effective nephroprotective interventions exist 2.