ALAD (aminolevulinate dehydratase) catalyzes an early step in heme biosynthesis by condensing two molecules of 5-aminolevulinic acid to form porphobilinogen 1. The enzyme functions as a zinc-binding protein involved in tetrapyrrole synthesis and exhibits proteasomal inhibitory activity through its role as an endogenous inhibitor of the 26S proteasome 2. ALAD deficiency causes ALAD porphyria, an autosomal recessive disorder characterized by marked reduction in ALAD enzymatic activity, leading to excessive urinary ALA excretion and acute hepatic symptoms resembling acute intermittent porphyria 1. Beyond porphyria, ALAD is clinically significant for its genetic polymorphisms affecting lead toxicokinetics. The ALAD G177C polymorphism (rs1800435) and related SNPs influence individual susceptibility to lead toxicity, with δ-ALAD-2 allele carriers showing altered lead binding and bioavailability 3. Additionally, ALAD polymorphisms interact with occupational lead exposure to modify prostate cancer risk 2 and influence mercury toxicity severity in exposed populations 4. ALAD genotype may independently affect mortality outcomes, with variant genotypes showing decreased all-cause mortality risk 5. These findings establish ALAD as a pharmacogenetically important gene for heavy metal susceptibility and environmental health.