MAN1A2 encodes mannosyl-oligosaccharide 1,2-α-mannosidase, a Golgi-resident enzyme that catalyzes progressive trimming of α-1,2-linked mannose residues from Man(9)GlcNAc(2) to produce Man(5)GlcNAc(2) during N-glycan maturation 1. Beyond its canonical glycosylation role, MAN1A2 has critical developmental functions. Genetic variants in MAN1A2 are significantly associated with biliary atresia, wherein man1a2 knockdown in zebrafish causes poor biliary network formation, ciliary dysgenesis, and hepatobiliary heterotaxy through dysregulated EGFR signaling pathways 2. Man1a2 knockout mice exhibit respiratory failure with reduced lung ciliation and portal inflammation 2. Gestational N-acetyl-cysteine treatment improves survival and lung ciliation in heterozygous Man1a2 mutants by mitigating oxidative and hypoxic stress 3. In cardiovascular disease, N-palmitoyl glycine promotes depression-associated atrial fibrillation by upregulating Man1a2 expression, reducing autophagy and disrupting intercalated disc integrity 4. MAN1A2 also shows non-linear associations with venous thromboembolism via endothelium development pathways 5, and genetic variants associate with SARS-CoV-2 infection susceptibility in Chinese populations 6. Clinically, MAN1A2 circular RNA dysregulation affects cisplatin chemotherapy sensitivity in esophageal squamous cell carcinoma 7.