NAT2*5 is assigned decreased function based on definitive evidence. The NAT gene nomenclature committee has historically assigned acetylation activity to alleles as either "rapid" or "slow", classifying the NAT2*5 allele as "slow" . Under the CPIC allele function terminology, slow acetylation alleles are categorized as "Decreased Function". The functional SNV c.341T>C (p.I114T) in NAT2*5 has been studied for more than 25 years and has shown decreased N-acetylation activity in numerous clinical and in vitro studies using various substrates. Clinical studies have demonstrated that individuals homozygous for NAT2*5 or heterozygous for NAT2*5 in combination with another decreased function allele exhibit decreased acetylation activity toward caffeine metabolites (8102597, 7668286, 10744128, 9891107, 20801937, 22970273, 24221535, 28653770), isoniazid (9154882, 9321764, 19336229, 35928262) sulfonamides (1872889, 15032315, 16570187, 18167504, 21946899), and dapsone (10762005). Individuals homozygous for NAT2*5 or heterozygous for NAT2*5 in combination with another decreased function allele exhibit increased hydralazine exposure (24702251, 31257615). Five out of nine variant effect predictors tested by CPIC staff predict that c.341T>C (p.I114T) impairs protein function. In vitro studies show that NAT2*5 exhibits similar thermostability to NAT2*4, which was previously used as the reference allele (8081359, 15564878, 17434923, 11337936), however NAT2*5 is subjected to enhanced protein degradation by the proteasome (15564878), indicating decreased protein levels as the molecular mechanism for the decreased acetylation activity observed.