AAAS encodes ALADIN, a nucleoporin essential for nuclear pore function and nucleocytoplasmic transport. The protein is required for proper development of the peripheral and central nervous system and ensures correct spindle formation during mitosis by localizing aurora kinase AURKA and the microtubule minus end-binding protein NUMA1 to the spindle pole [UniProt Function]. Biallelic mutations in AAAS cause Allgrove syndrome (Triple-A syndrome), an autosomal recessive disorder characterized by the cardinal triad of achalasia, alacrimia, and adrenal insufficiency (ACTH-resistant adrenal insufficiency) 1. Most pathogenic variants produce truncated proteins, though missense and point mutations have also been reported 1. Alacrimia is often the earliest and most consistent feature, while achalasia and adrenal insufficiency typically manifest early in life 1. Progressive neurological complications—including autonomic dysfunction, polyneuropathy, amyotrophy, and optic atrophy—emerge later, sometimes in the second or third decade 2. Management is symptomatic: glucocorticoid and mineralocorticoid replacement for adrenal insufficiency, artificial tears for alacrimia, and pneumatic dilatation or surgical myotomy for achalasia 1. At the population level, gnomAD v4.1 classifies this gene as LoF-tolerant (LOEUF=0.92); however, the 104 ClinVar pathogenic variants underscore clinical pathogenicity in disease contexts distinct from population-level constraint.