AMZ1 (archaelysin family metallopeptidase 1) encodes a zinc-dependent metalloprotease belonging to the archaemetzincin family. The protein contains a catalytic domain with a characteristic zinc-binding motif (HEXXHXXGX3CX4CXMX17CXXC) and demonstrates collagenase activity 1. AMZ1 is primarily expressed in liver and heart tissues, with functional protease activity confirmed through hydrolysis of synthetic substrates and bioactive peptides 1. Genetically, AMZ1 variants are significantly associated with normal pressure hydrocephalus (NPH) risk. A genome-wide association study identified the rs798495 SNP near AMZ1/GNA12 conferring increased NPH susceptibility (odds ratio 1.29, p=2.9e-12), with this association replicated in idiopathic NPH cohorts 2. Systematic review confirmed AMZ1 among multiple genes enriched for NPH risk variants, with these genes implicated in blood-brain barrier and blood-cerebrospinal fluid barrier function 3. Additionally, AMZ1 was identified within a 0.47 Mb overlapping deletion region on chromosome 7.3p22.2 associated with developmental delays and characteristic facial features 4, and rare AMZ1 copy number variants were detected in Turner syndrome patients 5. Clinically, elevated archaeal AMZ1 collagenase activity in extracellular microvesicles correlates with Chagas disease-associated heart failure, suggesting potential biomarker utility 6. However, the precise mechanistic role of AMZ1 variants in NPH pathogenesis remains unknown and warrants further investigation.