Lysinuric protein intolerance is estimated to occur in 1 in 60,000 newborns in Finland and 1 in 57,000 newborns in Japan. Outside these populations this condition occurs less frequently, but the exact incidence is unknown.

Mutations in the SLC7A7 gene cause lysinuric protein intolerance. The SLC7A7 gene provides instructions for producing a protein called y+L amino acid transporter 1 (y+LAT-1), which is involved in transporting lysine, arginine, and ornithine between cells in the body. The transportation of amino acids from the small intestine and kidneys to the rest of the body is necessary for the body to be able to use proteins. Mutations in the y+LAT-1 protein disrupt the transportation of amino acids, leading to a shortage of lysine, arginine, and ornithine in the body and an abnormally large amount of these amino acids in urine.

A shortage of lysine, arginine, and ornithine disrupts many vital functions. Arginine and ornithine are involved in a cellular process called the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is used by the body. The lack of arginine and ornithine in the urea cycle causes elevated levels of ammonia in the blood. Lysine is particularly abundant in collagen molecules that give structure and strength to connective tissues such as skin, tendons, and ligaments. A deficiency of lysine contributes to the short stature and osteoporosis seen in people with lysinuric protein intolerance. Other features of lysinuric protein intolerance are thought to result from abnormal protein transport (such as protein deposits in the lungs) or a lack of protein that can be used by the body (protein malnutrition).