The present technology is directed to compositions and methods for preventing, ameliorating, or reducing the severity of one or more signs, or symptoms associated with a reduction of function, decreased expression level of, and/or deficiency in one or more of COL4A3, COL4A4 and COL4A5 genes. Also disclosed herein are methods of preventing or treating Alport Syndrome in a mammalian subject, reducing risk factors associated with Alport Syndrome, and/or reducing the likelihood or severity of Alport Syndrome. The methods comprise administering to the subject an effective amount of an aromatic-cationic peptide.