Phenylalanine hydroxylase is an enzyme that catalyzes the rate limiting step in the catabolism of phenylalanine, thereby facilitating its clearance. Specifically, this enzyme catalyzes the conversion of L-phenylalanine to L-tyrosine. Phenylalanine is taken into the body by way of food, but instead of being used for protein synthesis, most of this amino acid is converted to tyrosine and undergoes further metabolism to form neurotransmitters and hormones. This conversion is very important, as shown by individuals in whom this mechanism is defective. Mutations in the PAH gene give rise to phenylketonuria (PKU), a condition in which pheylalanine accumulates to toxic levels in the blood and brain, resulting in severe consequences, including intellectual disability.

Mutations in PAH that cause complete reduction of the enzyme activity result in the classic or severe form of PKU, whereas other mutations that leave residual enzyme activity lead to milder versions of the condition, such as non-PKU hyperphenylalaninemia.